Taking place in person for the first time since 2019, the School of Public Health and Health Professions 15th annual Saxon Graham Lecture this year featured noted UB epidemiology alumnus Zuo-Feng Zhang, PhD 91, distinguished professor and chair of the UCLA Fielding School of Public Healths Department of Epidemiology, who discussed Challenges and Opportunity of the COVID-19 Pandemic on Non-communicable Disease Epidemiology.
Zhang, who is also a medical doctor, began by reviewing COVID-19 pandemic statistics infection rates and in the context of herd immunity and compared the United States to other countries.
As higher proportions of people gain immunity protection from vaccines and natural infection, we will see less transmission, much less hospitalization and death, even as the virus continues to circulate at a stable level of infection, he said.
Stay-at-home policies and masking continue to be protective, Zhang said, citing his own research on risk factors and his paper correlating smoking and air pollutant impacts on the SARS infection.
The risks apply to COVID-19 as well, with non-communicable diseases (NCD) such as cancer, cardiovascular and chronic lung conditions, and diabetes presenting significant severity and mortality rates in those infected with COVID-19. The highest risks are posed by high blood pressure, smoking and air pollution; overlapping factors and co-morbidities, including obesity, smoking and diabetes, further increase risks.
Zhang emphasized that while 80% of those who recover from COVID-19 will develop one or more long-term symptoms, 10 to 15 years of observation would be required to better understand the more than 60 potential long COVID symptoms, including the most common: fatigue, headache, brain fog, hair loss and shortness of breath.
Understanding the correlations between existing NCD and long-term COVID-19 symptoms, how vaccines will mitigate both infections and long COVID symptoms, and the interrelatedness of all risk factors, will all help to shape strategies for controlling both NCDs and COVID-19, Zhang said.
The Saxon Graham Lectureship honors the life and legacy of a man known as one of the fathers of U.S. chronic disease epidemiology, L. Saxon Graham, a longtime SPHHP professor and chair of the Department of Epidemiology and Environmental Health from 1981 to 1991. Zhang completed his PhD on cancer epidemiology and experimental pathology under Grahams mentorship.
STATEN ISLAND, N.Y. - They call us the forgotten borough. But Staten Island has had its share of earth-shaking moments that continue to shape us to this day.
Here are 15 of the most transformative happenings in borough history, in descending order.
Plans for a NASCAR track in Bloomfield were scrapped in 2006 after heated debate. (Advance file photo)
15. THE DEMISE OF NASCAR IN 2006
There was simply too much local opposition to the plan to build an 80,000-seat NASCAR racetrack in Bloomfield. Race-day traffic was the main concern voiced by Staten Islanders.
Mayor Bill de Blasio wrestles with Staten Island Chuck in 2014. (Advance file photo)
14. BILL DE BLASIO IS ELECTED MAYOR IN 2013
The ultra-lefty pol was never a fit for Staten Islanders. Crime exploded on de Blasios watch and his anti-car Vision Zero program earned him the enmity of all borough motorists. He also ate pizza for a fork and had a hand in the demise of one of our groundhogs. Even borough Democrats tired of de Blasio eventually.
Smoke billows from deadly LNG tank explosion in 1973. (Advance file photo)
13. THE DEADLY 1973 LNG TANK DISASTER
The explosion of empty liquefied natural gas tanks in Rossville in 1973 killed 40 workers and made Staten Islanders take a hard look at what types of facilities we would allow in our borough.
Remnants of New York Wheel project could still be seen long after its demise. (Advance file photo)
12. THE COLLAPSE OF THE NEW YORK WHEEL PROJECT IN 2018
The New York Wheel was supposed to lead a North Shore waterfront renaissance. But the project stalled after $200 million was spent at the site. It was a brutal reminder that big-ticket projects often face tough sledding on Staten Island.
Donald Trump in 2016 spoke to a packed ballroom at a GOP event in the Hilton Garden Inn in Bloomfield. (Advance file photo)
11. DONALD TRUMP IS ELECTED PRESIDENT IN 2016
Staten Island was the only borough to vote for Trump for president, underlining the red boroughs outsider status when it came to the rest of the city and state.
The shame and scandal of Willowbrook State School led to a revolution in how societies around the world care for mentally ill and disabled. (Advance file photo)
10. DISGRACE OF WILLOWBROOK STATE SCHOOL EXPOSED IN 1972
The Advance first detailed how those with mental disabilities were living in filthy, inhumane conditions at Willowbrook. It became a national disgrace that led to sweeping changes in the way that we treat the disabled. It was a horrific price to pay for reform.
In this 1994 photo Gov. Mario Cuomo, seated, has just signed a measure authorizing a study and initiating the process of Staten Island's secession from New York City. Shaking Cuomo's hand, left, is State Sen. John J. Marchi. Applauding the signing are, from the left, Assemblywoman Elizabeth A. Connelly, College of Staten Island president Edmond Volpe and assemblymen Robert Straniere and Eric Vitaliano. (Staten Island Advance/Irving Silverstein)
9. STATEN ISLANDERS VOTE TO SECEDE IN 1993
Fed up with being ignored by City Hall and Albany, and with our power diminished after the Board of Estimate was disbanded, Staten Islanders in 1993 voted in favor of a secession referendum that began the process of us leaving the other four boroughs and becoming an independent city. Assembly Speaker Sheldon Silver eventually killed the movement by insisting that the City Council issue a home-rule message on secession.
Jewett Avenue near the MTA bus depot was underwater as the remnants of Hurricane Ida passed over Staten island on Sept, 1, 2021. (Shared to @siadvance Instagram)
8. BOROUGH GETS WALLOPED BY HURRICANE IDA IN 2021
The intense storm flooded basements, backyards, roadways and the Staten Island Railway line, forcing Islanders to face the fact that our storm-sewer infrastructure just wasnt up to handling steadily worsening major storms.
The election of Rudolph Giuliani as mayor gave Staten Island outsized influence in city government for eight years. (Advance file photo)
7. RUDOLPH GIULIANI IS ELECTED MAYOR IN 1993
Staten Islands votes put the Republican over the top and Giuliani never forgot us. His partnership with GOP Borough President Guy Molinari led to what many consider a golden age of borough influence in city government. Giuliani also beat back crime and restored to prominence a city that many critics called ungovernable.
Remnants of abandoned subway tunnel are seen in this photo from 1937. (Advance file photo)
6. THE BROKEN PROMISE TO BUILD A SUBWAY HERE
Officials promised to build a subway line linking Staten Island to the rest of the city as an inducement for us to join the other four boroughs in the City of New York in 1898. While various holes were dug in the ground over the years, the subway line was never built. Its helped lead to overwhelming traffic congestion here that hurts Islanders quality of life every day.
Staten Island's coastal areas were among those hit the hardest by Hurricane Sandy. (Advance file photo)
5. HURRICANE SANDY DEVASTATES STATEN ISLAND IN 2012
Staten Islands coastal communities were among those that suffered the most from the superstorm, making us re-think how we develop our shorelines and highlighting the importance of maintaining woodlands and other open spaces that can soak up stormwater.
The 9/11 attacks killed 274 Island residents and left an indelible mark on the borough felt to this day. (Advance file photo)
4. TERRORISTS DESTROY THE WORLD TRADE CENTER ON SEPT. 11, 2001
No borough was hit harder by this national tragedy than Staten Island, which saw 274 residents killed on the actual day and has seen many more die over the subsequent decades due to 9/11-related diseases. None who were alive that day have ever forgotten it.
The final shipment of garbage arrived at the Fresh Kills Landfill on March 22, 2001. (Advance file photo)
3. THE FRESH KILLS LANDFILL IS CLOSED IN 2001
They said it couldnt be done. But after a fight led by Borough President Guy Molinari, the final barge of trash arrived at the landfill on March 22, 2001 and Staten Island finally was no longer the sole repository for all the citys garbage. An environmental crime from the day it opened, Da Dump was not only a blight on our landscape, but on our collective soul. The other four boroughs were never more uncaring of us.
COVID-19 public service sign on the West Shore Expressway during the early days of the pandemic. (Tom Wrobleski/Staten Island Advance)
2. THE COVID-19 PANDEMIC UPENDS LIFE BEGINNING IN 2020
We could hardly have known that wed still be battling the COVID-19 virus more than two years after the first cases were detected here. More than 2,300 Islanders have perished from coronavirus and untold numbers have had their work, school and social lives upended. Many who have recovered from the virus still feel the long-term effects. Battles over mask and vaccine mandates continue to divide us. We will always watch warily for the next wave of infections.
The opening of the Verrazzano-Narrows Bridge in 1964 changed Staten Island forever. (Advance file photo)
1. THE VERRAZZANO-NARROWS BRIDGE OPENS IN 1964
The seminal moment in the recent history of the borough. The opening of the bridge (spelled Verrazano-Narrows Bridge back then) kicked off a decades-long population explosion that helped fuel massive overdevelopment and resulting traffic congestion, crises that seem to still be worsening today.
Thanks for reading all the way to the bottom! Were there any big events that I missed here? Please write to me at wrobleski@siadvance.com. Thanks again for reading.
MORE STATEN ISLAND HISTORY FROM TOM WROBLESKI
From The Bridge to Below the Boulevard: 24 things that only true Staten Islanders know
How mob legend Lucky Luciano, the father of the modern Mafia, survived a one-way trip to Staten Island
Dan Aykroyd talks John Belushi and cocaine-fueled 1980s movie shoot on Staten Island
Recall these vintage shops, patriotic moments and small-town sights of Main Street in Tottenville?
Husband smiles for the camera after bludgeoning unfaithful wife to death in Staten Island motel in 1962
Haunted Silver Lake: Islander slays wife in infamous 1878 beer-barrel murder
How Staten Island helped catch Son of Sam in the summer of 1977
One tragic fact about the nearly 1 million people who died of COVID-19 in the U.S. is that a huge share of them didn't have to.
In Tennessee, 11,047 of the people who died could have survived if everyone in the state had gotten vaccinated. In Ohio, that number is 15,875. Nationally it's nearly 319,000, according a new estimate.
These figures come from an analysis released Friday by researchers at Brown University and Microsoft AI Health shared exclusively with NPR that estimates the portion of vaccine-preventable deaths in each state since COVID-19 vaccines became available at the start of 2021.
In early 2021, when the vaccines were widely distributed, there was huge demand. At the peak of the vaccination campaign in the spring, 4 million people got vaccinated in one day. That demand dropped off by summer. A year later, many states are still barely north of 50% of people fully vaccinated.
How many lives would have been saved if that slump in vaccine demand had never happened? To answer that question, Brown and Microsoft researchers calculated the peak vaccination rate for each state, and then imagined that rate continued until all adults in the state were fully vaccinated.
The total for the country is stark: Many of the nearly 1 million COVID deaths took place in 2020 before the vaccines were available. But of the more than 641,000 people who died after vaccines were available, half of those deaths could have been averted 318,981 had every eligible adult gotten vaccinated. And those numbers are even more striking in certain states where more than half of deaths could have been avoided.
"The vaccine rollout has been both a remarkable success and a remarkable failure," says Stefanie Friedhoff, a professor at the Brown School of Public Health, and one of the analysis's authors. It was a success, she says, in the sense that "the United States was first in getting those vaccines developed and making doses available at high numbers quickly to the public."
A lot of money and energy was invested in the logistics of the rollout the supply side of the equation. Much less was invested in encouraging vaccine demand, she says.
"We did not start early on with information campaigns about why vaccines are important what do they do for us?" she says. "We underestimated dramatically the investment it would take to get people familiarized with vaccines because, by and large, we haven't had a deadly disease like this, so people have become estranged from the important impact of vaccination."
The map of states with the most preventable deaths shows a sharp political divide as NPR has reported, people living in counties that voted for then-President Trump in the 2020 election were three times more likely to die from COVID-19 than people who lived in counties that voted for President Biden.
According to the analysis, West Virginia, Wyoming, Tennessee, Kentucky and Oklahoma had the most vaccine-preventable deaths per capita. Washington D.C., Massachusetts, Puerto Rico, Vermont and Hawaii had the fewest.
The analysis is accessible in an interactive dashboard showing different scenarios to estimate the impact of vaccines state by state, such as a vaccination rate of 85% or 90% instead of 100%.
The national number of vaccine-preventable COVID deaths calculated by Brown and Microsoft exceeds an earlier analysis from the Kaiser Family Foundation, which put that number at 234,000. Cynthia Cox, director of the Peterson-Kaiser Health System Tracker and a co-author of that analysis, tells NPR that differences in methodology may explain the discrepancy.
Unlike the KFF analysis, the new analysis included data on how many Americans were boosted so the vaccine-preventable death total includes people who never got vaccinated, along with those whose vaccine protection had waned and who had not received a booster.
Of the Brown research, Cox says, "I think this is a really clear way of demonstrating both the effectiveness of vaccines and also the need to continue to vaccinate more people and to make sure that they're up to date on those vaccines."
She notes one limitation is that the calculations may be overestimating the impact of vaccines, since the mostly Republican-led states that had lower vaccination rates also underused other pandemic-fighting tools, such as mask and social distancing requirements.
One state that stands out in the analysis is West Virginia, says Dr. Thomas Tsai, a surgeon and professor at Harvard School of Public Health and co-author of the analysis with Friedhoff.
Early on, West Virginia's vaccine rollout was celebrated as other states struggled to take a stockpile of vaccines and get them into people's arms.
"There was a very, very early push to get vaccinations out, but a lack of resources to see it through the course of the year," Tsai says. "West Virginia could have ended up like Maine or Vermont, but ended up being more like Wyoming or Idaho not for lack of effort, potentially, but for lack of resources."
A. Toni Young runs a public health outreach organization in West Virginia called Community Education Group, that has worked to vaccinate people against COVID-19 across the state. From her perspective, the drop in the vaccination rate came when the voices of local pharmacies and physicians were overpowered by national voices denying the seriousness of COVID-19 or saying that herd immunity was imminent.
"Folks started to have a conversation within their social networks, and had a real attitude of, 'Well, someone else has been vaccinated, I don't need to be vaccinated.' They also started to see people, particularly in a younger age cohort, get COVID and survive," Young says.
"I think that we could have had more trusted leaders doing the messaging in West Virginia," Young adds.
"All of this comes down to trust whether the political leadership creates the climate of trust in the public health agencies' efforts, in the science, in the ability of the health care system to deliver," Tsai says. "To me, this is a map of trust."
A senior White House official speaking with NPR on background pointed to work the administration has done to invest in community-led vaccination efforts, and said that trust-building was a key part of what the Biden administration is asking Congress to fund.
But the push for more federal COVID-19 funding appears to be stalled. The White House has been asking for $22.5 billion when Congress got close to a funding deal in April, it would have been for less than half of that. Federal officials warn that this delay could affect Americans' access to booster shots in the future. Funding for free COVID-19 vaccination, testing and treatment for people without health insurance has already run out.
The patterns found in the Brown analysis could well continue with future COVID deaths piling up in places where vaccination access is poor and hesitancy is high, cautions Friedhoff.
Immunity both from vaccines and prior infection appears to wane over time and further booster campaigns could well be needed to save lives.
"We're at a point where we have 1 million deaths, but also very little investment and interest in continuing vaccination campaigns and continuing the support for vaccination," she says. The data underlying this tool is real, she notes the people who actually got vaccinated and the people who actually died. "The basis for this dashboard is what actually happened, and it can show us in spite of all the narratives how many people didn't have to die."
It provides evidence and incentive, she adds, to try and support more people in the decision to get vaccinated.
RICHLAND A federal judge has dismissed a lawsuit brought by several hundred Hanford nuclear reservation and Pacific Northwest National Laboratory workers in Richland, Washington, over COVID-19 vaccine requirements.
The lawsuit was filed in November to halt enforcement of President Joe Bidens executive orders requiring COVID-19 vaccinations for Department of Energy employees and the employees of contractors and subcontractors on federal projects, The Tri-City Herald reported.
But U.S. Judge Thomas Rice found that lawyers for the Hanford and national lab workers had not provided clear arguments nor specific information about most workers to make their case.
With the original complaint already changed once, Rice had no confidence in another amended complaint after their continued failures to address the shortcomings in their various pleadings, he said in his order dismissing the case. The case has been argued by Nathan Arnold of Seattle and Pete Serrano, a Pasco city council member and director and attorney for the Silent Majority Foundation in Pasco, which organized the lawsuit.
Rice had already refused to temporarily halt enforcement of the vaccine mandates while the lawsuit proceeded. The judge said 307 of the workers in the case had not shown they were harmed by the vaccine mandate or that a decision in their favor would redress any harm.
Many had not filed for religious or medical exemptions allowed by the mandates, Rice said. Others had filed but failed to provide information to the court on their exemption or vaccination status.
Without knowing whether these plaintiffs are in compliance with the vaccination or exemption requirements, it is impossible to know whether they could face an adverse employment action, Rice said.
Other plaintiffs failed to say who employed them, giving them no standing in the case. That left just seven plaintiffs in the case with possibly valid claims.
Attorneys argued that the vaccine mandates violated the U.S. Constitution. But Rice found that a closer examination of the claims reveals only broad recitations of various constitutional principles muddled with repetitive allegations that the executive orders were promulgated in excess of President Bidens authority.
Claims based on freedom of religion did not hold up because plaintiffs did not identify the religious activities they were engaged in or how those activities were substantially burdened by the executive orders, Rice said. Rice also found that the vaccine mandates or a valid exemption were a requirement for employment, but no one had been forced to get a vaccine, he said.
DOE hires contractors to do most of the work at the Hanford site, with the large majority of the 11,000 workers at the nuclear reservation employed by contractors and subcontractors. The claimants in the lawsuit included some DOE employees, but mostly contractor and subcontractor employees.
The 580-square-mile (1,502-square-kilometer) Hanford nuclear reservation in Eastern Washington was used from World War II through the Cold War to produce nearly two-thirds of the plutonium for the nations nuclear weapons program.
About $2.5 billion annually is spent on environmental cleanup of the contaminated site. Pacific Northwest National Laboratory is a Department of Energy Office of Science laboratory in Richland operated by Battelle under an Energy Department contract. It employs about 5,350 people and has an annual budget of about $1.25 billion.
The second Global COVID-19 Summit, co-hosted by United States, Belize, Germany, Indonesia, and Senegal, convened over partners and organizations from around the world to accelerate collective efforts to get shots into arms, enhance access to tests and treatments, protect the health workforce, and finance and build health security for future pandemics and other health crises.
The Summit garnered new financial commitments totaling $3.2 billion, not yet announced, above and beyond pledges made to date in 2022. This includes nearly $2.5 billion for COVID-19 and related response activities and $712 million in new commitments toward a new pandemic preparedness and global health security fund at the World Bank. (Note: This builds on $250 million previously pledged for this fund.) We encourage partners to join, as much more is needed to control COVID-19 and build better health security.
Commitments[1] from Government, Other Partners, and Entities
Note: Country text is being validated with host governments and is not yet final.
Commitments[2] from Non-Governmental Organizations, Private Sector, Philanthropies
In addition, we have received commitments from more than 50 organizations, including local and international non-governmental organizations, businesses, philanthropies, advocacy groups, faith-based organizations, and other members of civil society. To date, new commitments in 2022 outlined below exceed $700 million for vaccinating the world, saving lives now, and building better health security.
[1] All commitments made in 2022 are counted toward the goals of the 2nd Global COVID-19 Summit. Of these, approximately $3.1 billion were raised in new funds, not yet announced.
[2] All commitments made in 2022 are counted toward the 2nd Global COVID-19 Summit. Of these, approximately $700 million was raised in new funds, not yet announced.
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WASHINGTON President Biden and other leaders issued an urgent call on Thursday for the world to step up its fight against Covid-19, and countries including Germany, Canada and Japan pledged large sums to finance tests, therapeutics and vaccines a commitment Mr. Biden could not make because Congress has refused to authorize new pandemic aid.
As the United States approached a harrowing milestone one million American lives lost to the virus fear of another deadly variant loomed large over the presidents second global Covid-19 summit, a virtual gathering co-hosted by Belize, Germany, Indonesia and Senegal. But some countries were notably absent. China, in the thick of its own Covid crisis, did not attend. Russia, waging war against Ukraine, was not invited.
Senior Biden administration officials said the summit produced more than $3 billion in commitments toward the global response and toward efforts to prevent future pandemics. That is far short of the $15 billion that the World Health Organization says is needed. But the summit did lay the groundwork for a new global preparedness fund.
The gathering on Thursday unfolded in a very different climate compared with that of the first Covid summit in September. The war in Ukraine is sapping energy and money from donor nations. The global vaccination campaign has stalled. Testing has plummeted around the globe. Covid antiviral pills, available in the United States, are scarce in many low- and middle-income nations. Many attendees said Covid fatigue had become as big a danger as Covid itself.
Theres still so much left to do; this pandemic isnt over, Mr. Biden said in his opening remarks, adding, We have to prevent complacency.
But the presidents tone was tepid compared with that of some of the other participants, who included heads of state, global health officials and philanthropic leaders. Several, including Dr. Joy St. John, the executive director of the Caribbean Public Health Agency, said climate change was speeding up the cycle of pandemics, making the next outbreak inevitable.
The next virus may kill even more people and cause even greater economic disruption, she warned.
Bill Gates, the software entrepreneur and philanthropist whose foundation has donated tens of millions of dollars to pandemic relief efforts and who tested positive for the coronavirus this week railed against global health inequities.
We need to make more lifesaving tools and allocate them based on need rather than wealth, Mr. Gates declared, adding, We dont have time to waste.
There were some proverbial elephants in the room: Chinas ongoing Covid crisis and the war in Ukraine were not discussed. But J. Stephen Morrison, an expert in global health at the Center for Strategic and International Studies, said the commitments by Group of 7 nations reflected the strengthening of bonds between countries allied against Russia in the Ukraine war.
Those pledges, he said, will pave the way for the World Bank to create a new global pandemic preparedness fund. The fund will be similar to the Global Fund to Fight AIDS, Tuberculosis and Malaria, which was created two decades ago.
It was the G7 that was the core of the H.I.V. response, and in some ways this is getting that same garage band back together, Mr. Morrison said. Referring to the lack of congressional funding, he said, Overall, not a bad outcome given the circumstances.
Before the summit began, Mr. Biden ordered flags lowered to half-staff at the White House and all public buildings and military installations until Monday in commemoration of the nations death toll.
As of Wednesday, the Centers for Disease Control and Prevention had reported more than 995,000 coronavirus deaths in the United States; a New York Times database put the figure at more than 997,000. But with heads of state, leaders of philanthropies and pharmaceutical executives attending the virtual gathering, Mr. Biden was ready to mark the coming moment.
Globally, the World Health Organization has said that nearly 15 million more people died during the first two years of the pandemic than would have been expected during normal times. That estimate far exceeds the official Covid death toll reported by countries.
Despite the gloomy predictions, summit participants did report some progress. Samantha Power, the administrator of the U.S. Agency for International Development, told attendees that in Ghana, the percentage of eligible people fully vaccinated had doubled between December and April and now stood at 25.4 percent. Uganda has also seen a surge in vaccination.
Now is not the time to back down; it is the time to push ahead, she said, even if this fight may drag on longer than any of us want.
The White House instructed participants to come to Thursdays summit with significant commitments either financial or nonmonetary. One by one, over the course of four virtual sessions, philanthropies and drugmakers stepped up.
Chancellor Olaf Scholz of Germany pledged $1.5 billion, saying his country wants to lead by example. Prime Minister Justin Trudeau of Canada said his country would donate $732 million. South Korea offered $300 million.
The Clinton Health Access Initiative said it had negotiated agreements with drug manufacturers to make generic versions of Pfizers Covid antiviral, Paxlovid, available for less than $25 per course. Merck, whose Covid antiviral, molnupiravir, has already been distributed in generic form in 15 countries, said it would make two million courses of the drug available at a best access price to low- and middle-income nations.
The United States, which has already committed $19 billion to the global response, did not come entirely empty-handed. The Biden administration put forth a relatively small amount of money at the meeting: $200 million for the World Bank fund to prepare for future pandemics and $20 million for pilot projects to bring coronavirus tests and treatments to poor nations.
But that is much less than Mr. Biden hoped for. The president has asked Congress for $22.5 billion including $5 billion to fight the pandemic globally in emergency coronavirus aid, but the proposal is stuck on Capitol Hill, even as Congress hurries to approve $40 billion in emergency aid for Ukraine.
Lawmakers are still struggling to figure out how to advance a pared-down $10 billion coronavirus package. A group of Nobel laureates and former heads of state, including former Prime Minister Gordon Brown of Britain, called this week for Congress to fulfill Mr. Bidens request.
Weve got to puncture the complacency about this, to make sure that people realize that if we dont act, another variant is a possibility and we dont know how lethal it could be, Mr. Brown, who is now the World Health Organizations ambassador for global health financing, said in an interview this week.
The United States also made a significant nonmonetary commitment: The National Institutes of Health has agreed to license its stabilized spike protein technology a crucial component of Covid vaccines and treatments to companies through the Medicines Patent Pool, a global nonprofit backed by the W.H.O. that works to bring medicines to low- and middle-income nations at low cost.
The move is significant because it may lay the groundwork for other countries and companies to share their technologies, said Peter Maybarduk, who directs the global access to medicines program for Public Citizen, a consumer advocacy group, and serves on the patent pools board.
While the United States has donated hundreds of millions of vaccine doses to poor nations, it has been less aggressive about sharing technology.
One of the terrible injustices and major impediments in this pandemic has been the exclusive control of critical medical technology, Mr. Maybarduk said. By working with the Medicines Patent Pool, he said, the Biden administration would be not only sharing doses, but sharing knowledge, on the view that sharing doses is charity and sharing knowledge is justice.
May 12, 2022
An earlier version of a picture caption with this article misspelled the name of a town where a booster shot was administered in Sri Lanka. It was Kalawana, not Kalwana.
Since the initial global outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, a continuous evolution of the virus has been observed. The emergence of new SARS-CoV-2 variants, which have been classified as variants of concern (VOC) and variants of interest (VOI), has reduced the efficacy of the COVID-19 vaccines and has, therefore, fuelled the pandemic situation.
Previous studies have reported that mRNA-based COVID-19 vaccines effectively elicit robust antibody and T cell responses, and protect individuals from SARS-CoV-2 infection. However, the incidence of breakthrough infections related to the Omicron variant and the waning of vaccine-induced neutralizing antibodies has led to the development of the COVID-19 booster vaccination strategy.
Several studies have reported the immediate benefits of COVID-19 booster immunizations, with respect to neutralization capacity against SARS-CoV-2 variants. However, there is a lack of data regarding the effect of the mRNA booster vaccine on the spike-specific CD8+ T cell response.
Additionally, not much evidence has been documented regarding the effectiveness of the three-dose vaccine regimes, their response to the breakthrough infection, and the duration of immune protection.
A new preprint study, posted on Research Square*,addressed the aforementioned gap in research and has longitudinally traced and profiled the CD8+ T cell responses after COVID-19 mRNA booster vaccination.
Scientists recruited thirty-eight individuals, from the Freiburg University Medical Center, Germany, who were immunized with the COVID-19 mRNA booster vaccine. They obtained blood samples from thirty-one individuals who received three doses of one of two mRNA vaccines, namely, BNT162b/Comirnaty or mRNA-1273/Spikevax vaccine.
Scientists reported that the study cohort included five participants who received four doses of the vaccine and were without a history of COVID-19 infection. Thirteen participants had a history of breakthrough infection after the third dose of a booster vaccination. All participants with breakthrough infection after booster vaccination exhibited mild symptoms without respiratory insufficiency.
In this study, the authors analyzed spike-specific CD8+ T cell responses, on a single epitope level, in participants who received COVID-19 mRNA-based booster vaccination (third and fourth) after four months of the third dose and one-two months post the fourth vaccination regime. The authors also evaluated spike-specific CD8+ T cell responses in breakthrough infections with the Omicron and Delta variants, post booster vaccination.
Researchers reported a fast and vigorous increase of spike-specific CD8+ T cell responses after third and fourth doses of the vaccine, with respect to breakthrough infection with the Delta and Omicron variants. Scientists reported that the magnitude and kinetics of immune response of this study cohort were similar to the spike-specific CD8+ T cell response after the second dose of the COVID-19 vaccine. This was observed by detecting a high level of expression and proliferation of CD38 and Ki-67. This finding strongly supports the rapid induction of functional CD8+ T cell responses after COVID-19 mRNA vaccination.
Scientists reported that the spike-specific CD8+ T cell booster responses after third and fourth doses of COVID-19 booster vaccination declined after around one to two months and, subsequently, reached a concentration similar to prior booster vaccination. This observation is extremely important and should be considered while formulating the booster vaccination strategy. Interestingly, in contrast to the steep waning off of the spike-specific CD8+ T cell boost response, a prolonged contraction after natural infection, irrespective of the infecting variant, has been observed.
A previous study reported the prolonged contraction of non-spike epitope-specific CD8+ T cells after COVID-19 infection. These differences in antigen half-life, antigen presentation, cytokines, innate immunity, and CD4+ T cell responses might be due to differences in responses after mRNA vaccination and COVID-19 infection. Therefore, there is a need for a better understanding of the interactions of immune components during natural infection and their responses post-vaccination.
In this study, researchers reported that the promising spike-specific CD8+ T cell memory response is not significantly affected by the third dose of vaccination. The current study revealed that the third dose did not augment long-term CD8+ T cell immunity and had no influence on the senescence of the CD8+ T cell memory pool. This finding is consistent with a previous study that reported antigen exposure does not cause T cell exhaustion of spike-specific CD8+ T cells. Researchers believe that the spike-specific CD8+ T cell booster response is an effector response that is based on a stable memory pool.
The authors revealed that mRNA booster vaccination is a powerful tool that can induce rapid and functional CD8+ T cell responses, which can be extremely beneficial to immediate alleviation of high viral burden. This strategy could effectively protect the vulnerable population and reduce the overwhelming burden of the healthcare system. However, the rapid decline in the spike-specific CD8+ T cell response hasto be considered while formulating the COVID-19 booster vaccination strategy.
Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Coronaviruses belong to the Coronaviridiae family in the Nidovirales order. Bats were considered to be the only reservoir, and the first animal to be documented was the Chinese horseshoe bats [1-3]. The human-to-human transmission of the virus occurs due to close contact with infected persons, and aerosols generated during coughing or sneezing can penetrate the human body during inhalation through the nose or mouth [4]. The earliest case was documented in December 2019, and it is the seventh member of the coronavirus family to infect humans [5]. The International Committee on Taxonomy of Viruses (ICTV) named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease coronavirus disease 2019 (COVID-19). The higher transmission rate of SARS-CoV-2 could be a genetic recombination event at the S protein in the RBD region [4]. The virus undergoes mutations resulting in variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617 (delta), and the newer variant omicron (B.1.1.529). Omicron has more than 30 deletions and is considered to be a heavily mutant variant that reduces vaccine-mediated immunity [6]. Vaccines are the only tool to control this pandemic outbreak as no specific therapies have been introduced to date. Numerous vaccines have been manufactured, and this article provides information about COVID-19 vaccines and their efficacy against coronavirus variants.
Coronavirus is an enveloped virus approximately 120 nm in diameter with a single-stranded RNA genome. The RNA genome consists of a 5 methyl-guanosine cap, poly (A) tail, and 29,903 nucleotides. It consists of an open reading frame (ORF) encoding non-structural proteins for replication, four structural proteins (spike, envelope, membrane, nucleocapsid), and numerous accessory proteins. The spike glycoprotein binds to angiotensin-converting enzyme 2 (ACE2) in humans for cell entry. The spike protein is cleaved by host proteases into S1 and S2 subunits where S1 is responsible for receptor recognition and S2 for membrane fusion. S1 can be divided into the C-terminal domain and N-terminal domain, with the C-terminal domain showing a stronger affinity for human ACE2. After attachment, the conformational change in the S protein facilitates the fusion of the virus envelope with the cell membrane. The viral RNA genome is released into the cytoplasm and translated into viral replicase polyproteins pp1a and pp1ab3 which are cleaved into small products by virus-encoded proteinases. The polymerase transcribes a series of subgenomic mRNAs by discontinuous transcription which are finally translated into viral structural proteins (S, E, M, N proteins). The N protein combines with the positive-stranded genomic RNA to form a nucleoprotein complex. The structural protein and nucleoprotein complex are assembled within the viral envelope and then released from the infected cell [5].
The glycoprotein spikes on the outer surface of the virus are responsible for the attachment and entry of the virus into host cells. The receptor-binding domain (RBD) is loosely attached among viruses and this is how it infects multiple hosts. Coronavirus depends on cellular proteases such as human airway trypsin-like protease (HAT), cathepsins, and transmembrane protease serine 2 that split the spike protein and help in further penetration. Research on animal studies has revealed that mutation atspike glycoprotein is responsible for severe infection and that therapeutic agents must target spike glycoproteins
Broad-spectrum antibiotics and antiviral drugs were initially used; however, remdesivir has shown promising results. The blood plasma from recovered patients has been injected into infected patients and has shown rapid recovery. Monoclonal antibodies (CR3022) had been found to bind with the spike RBD of SARS-CoV-2 without overlapping with the ACE2 receptor-binding motif. The major hurdle in creating a vaccine is to overcome cross-resistance. Many companies such as Moderna Therapeutics, Inovio Pharmaceuticals, Novavax, Vir Biotechnology, Ster Mirna Therapeutics, Johnson & Johnson, VIDO-Intervac, GeoVax-BravoVax, Clover Biopharmaceuticals, Curevac, and Codagenix had been working for the development of vaccines against COVID-19 [4].
RNA/DNA Vaccines
It uses the host cells transcription and translation processes to express the vaccine antigen that is encoded by the injected nucleotide. COVID-19 RNA-based vaccines are delivered in lipids, and the production is a very quick process [7]. However, freezing huge amounts of the vaccine is challenging [8]. The mRNA-1273 vaccine administered in lipid particles that encode for spike protein triggered a good antibody response [9].
Viral Vector-Based Vaccines
The genetic sequence of the foreign viral antigen inserted into the genome is the baseline of viral vector vaccines. This antigen is either secreted inducing B-cell/antibody response or digested within the target cells inducing a potent CD8+T cell response [10]. However, the vaccine could be neutralized if the vaccinated individuals have pre-existing antibodies against the vector virus. The recent viral vector vaccine against COVID-19 is mostly adenovirus-based. Antibody and T-cell responses were increased on day 28 after vaccination even after its reduction with the presence of pre-existing anti-adenovirus antibodies [11]. ChAdOx1, also known as AZD1222 (Covishield), has increased antibody titers after a booster dose at 28 days [12].
Protein-Based Vaccines
Protein-based vaccines/inactivated vaccines with aluminum salt adjuvants are currently used in routine childhood immunization. One such vaccine for COVID-19 is PiCoVacc, also called CoronaVac, for which clinical trials are ongoing in healthy individuals and the elderly population [13,14]. -propiolactone inactivated SARS-CoV-2WIV04 is another alum-adjuvanted strain with more antibody titers, but these types of vaccines have a chance of eliciting antibody enhancement of disease [15,16]. The other adjuvant vaccines in the trial are the adjuvanted S-trimer vaccine (SCB-19) and subunit vaccine NVX-CoV2373 adjuvanted with matrix-M1 saponins [17].
Vaccines Based on Accentuated SARS-CoV-2 Viruses
This is the most traditional technique where the virus has been weakened so that it will not cause the disease. Though it is effective in strengthening the immune system and inducing a strong immune memory, none of the vaccines for COVID-19 have reached the stage of clinical trials [18].
Vaccines Based on Inactivated SARS-CoV-2 Viruses
This vaccine is based on killed viruses but has a short immune memory. This is not only designed to direct against the spike protein but also many other SARS-CoV-2 antigens. CoronaVac and Sinopharm from China and Covaxin from India were successfully administered to the population after completing phase III trials [18].
Vaccines Based on SARS-CoV-2 Proteins
The vaccines are based on the proteins present on the surface of microbes that are produced in vitro with the help of DNA recombinant technology. The targets of these vaccines are the spike protein and, to some extent, nucleoprotein. Novavax from the United States and Co-VLP have completed phase III trials and have been administered to the population in two doses [18].
Naked DNA-Based Vaccines
DNA plasmids enter human cells after vaccination and induce cells to produce the target protein for a while, thus stimulating the production of antibodies and activation of killer T-cells. Although DNA vaccines are used in the veterinary field, none of them have been administered to humans. However, Inovio from the United States and Genexine from Korea are under trial [18].
mRNA-Based Vaccines
mRNA vaccines induce the cell to produce antigen proteins coded by the mRNA where it is carried by liposomes as nanoparticles, unlike DNA-based vaccines. Pfizer from the United States, Moderna from the United States, Arcturus Ther from Singapore, and CureVac from Germany have been administered to the population after passing clinical trials successfully [18]. In addition, an inhaled form of vaccine from the University of Oxford, UK, has not yet reached phase III trial.
Vaccines Based on Viral Vectors
The DNA coding for the spike protein is inserted into the virus as the virus has the ability to induce immunity by delivering mRNA into the cells. Sputnik from Russia, Covishield from India, Johnson & Johnson from the United States, and Ad5-nCoV use viral vectors to target spike protein [8].
Vaccine efficacy is generally reported as relative risk reduction (RRR) which uses the relative risk (RR) that uses the ratio of attack rates with or without a vaccine, whereas absolute risk reduction (ARR) uses the whole population. However, ARR tends to be ignored as it gives much less effect than RRR. Efficacy provides the RRR of 95% for the Pfizer-BioNTech, 94% for Moderna-NIH, 91% for Gamaleya, 67% for Johnson & Johnson, and 67% for AstraZeneca Oxford vaccines. However, the spectrum entirely changes when the effectiveness of a vaccine is calculated in terms of the number needed to vaccinate (NNV) to prevent one more case of COVID-19, with 81 for Moderna-NIH, 78 for AstraZeneca Oxford, 108 for Gamaleya, 84 for Johnson & Johnson, and 119 for Pfizer-BioNTech vaccines [19].
BNT162b2/Pfizer/BioNTech was the first vaccine approved by the European Medicines Agency against COVID-19 which is administered intramuscularly after dilution in a cycle of two doses 21 days apart [20,21]. Preclinical data include the investigation of immunogenicity and antiviral properties in mice and non-human primates, which proved that the BNT162b2 vaccine protected the lungs of immunized rhesus macaques from COVID-19 [22]. In a phase I/II study, where BNT162b2 was administered to adults, the geometric mean concentrations of RBD-binding immunoglobulin G (IgG) were high after 21 days of the first dose (534-1778 U/mL) when compared to the human convalescent serum (HCS 602 U/mL) after 14 days of the infection confirmed by polymerase chain reaction (PCR). This vaccine showed 95% efficacy and proved that early protection occurs 12 days after the first dose. Another study was performed to evaluate the humoral and adaptive immune response for BNT162b1 from phase I/II studies, in which GMC of anti-RBD antibodies were more in vaccinated individuals (3,920-18,289 U/mL) when compared to HCS (602 U/mL) [23,24]. Further, the efficacy of the vaccine against variants was also tested which shows high neutralizing capacity in all variants, with increased CD4+ and CD8+ RBD-specific T-lymphocytes [25]. However, BNT162b2 was recommended as it is associated with lower incidence and severity of systemic complications when compared to BNT162b1. A two-dose regimen of BNT162b2 conferred 95% efficacy against COVID-19 in a study conducted among 43,448 participants who were injected with the COVID-19 vaccine and saline placebo. Though the efficacy after the first dose was only 51%, it gradually increased to 91% within the first seven days of the second dose [26]. The vaccine efficacy among participants with hypertension also yielded an efficacy of 94.6%, consistent with other participants [27]. Another study amonghealthcare workers in Israel to evaluate the efficacy was found to be 30% in 1-14 days and 75% in 15-28 days [27-29]. In another study, the efficacy in preventing hospitalization after severe infection was found to be 80%, and a single dose helped in preventing death by 85%[30-32].
The Sputnik V vaccine is a vector vaccine based on adenovirus DNA administered over a course of two days, initially produced in Russia. In the previous study, the efficacy of the Sputnik vaccine with two vector components, namely, recombinant adenovirus type 26 (rAd26) and adenovirus type 5 (rAd5), manufactured in two formulations - frozen (0.5 mL) and lyophilized (1 mL of sterile water per dose) was demonstrated. There was increased production of CD4+ and CD8+ after administration of the frozen form than of the lyophilized form, and there was also increased production of interferon-gamma (IFN-) in all vaccinated individuals. The titer of neutralizing antibodies matches the convalescent human serum of those who recovered from recent infection [33]. The phase 3 trial of the Sputnik vaccine gives an efficacy of 91.6% (confidence interval (CI) = 95%), and, interestingly, it was 91.8% for older adults above 60 years. However, initially, the efficacy was 73.6% till 21 days after the first dose [33,34]. In another study where the vaccine was administered in older individuals after the first dose, the efficacy was found to be 78.6% of laboratory-confirmed SARS-CoV-2 infections, 94% in hospitalization, and 93% in preventing death among them, thus delaying the second dose can be followed to increase neutralizing antibodies [35]. The vaccine resists the variants of the COVID-19 virus with a 6.1-fold reduction in the neutralizing activity [36].
Covishield/AZD1222/ChAdOx1 is a viral vector intramuscular vaccine manufactured by the Serum Institute of India and is administered in two doses. In a study among 52 healthy individuals who received the second dose after 56 days of the first dose, there were no systemic reactions such as pyrexia as in the first dose [37-39]. After the first dose, discrete populations of T-cells, B-cells, and natural killer (NK) cells were detected. There was no sex difference and association between the age and magnitude response in this study among individuals aged from 18 to 55 years. The IgG spike was similar to that of plasma from convalescent patients with SARS-CoV-2. The CD4+ and CD8+ secrete antigen-specific cytokines with CD8+ T-cells expressing CD107a, which is a degranulation marker, indicating its cytotoxic effect after vaccination. However, the predominant cytokines were IFN- and CD8+ cells [38]. The levels of anti-spike IgG were found to be lower when the individuals received half-booster doses; however, it was increased to 10-fold when they received prime booster doses [38,39]. The total antigen-specific T-cell response was increased after 14 days of vaccination [37]. The second dose either given after 28 days or 56 days after the first shot provides a similar response in producing the antibodies [39]. Preclinical studies in Rhesus macaques prevent SARS-CoV-2-mediated pneumonia [40]. After administration of Covishield with booster dose in older adults, microneutralization assay peaked by day 42, the antibody titers were not raised after the booster dose in all age groups, and the immunization response in older adults was very similar to young adults. The anti-spike IgG levels correlate with neutralizing antibody titers for all age groups (18-55, 56-69, 70, and older) [41]. Another study with 23,848 participants across different parts of the world such as the UK, Brazil, and South Africa was conducted to estimate the efficacy. Interestingly, those who received two standard doses had lesser efficacy (70.4%) than those who received a low dose (2.2 1,010 viral particles) vaccine at the first dose followed by the standard booster dose (5 1,010 viral particles) (90%). The second dose within six weeks of the first dose provides less efficacy (53.4%) than the one with more than six weeks between the first and second dose (65.4%). Thus, delaying the second dose helps in increasing the efficacy, as well as overcoming the low availability of vaccines in this pandemic situation [42].
Covaxin/BBV152 is an inactivated virus-based COVID-19 vaccine formulated by Bharat Biotech and administered intramuscularly in two doses similar to any other COVID-19 vaccine. In a study with 375 healthy individuals, the vaccine (3 g and 6 g with IMBG) was given randomly to evaluate the immune response and efficacy. The most common adverse effects reported were pain in the injection site (5%), fatigue (3%), and headache (3%). The IgG titers were increased after the second dose, and the efficacy was 87.9% with 3 g and 91.9% with 6 g, thus IgG titers do not have any effect on the concentration [43]. However, both the doses elicit CD3+, CD4+, and CD8+ leading to IFN- production, and the neutralizing antibodies remained elevated for three months after the second vaccination. In the follow-up study with 380 participants, the neutralizing antibody titers were similar to the convalescent serum, and the same results were obtained in other studies [31,44,45].
The Janssen/Johnson & Johnson is another viral vector-based vaccine that requires only a single dose. The first dose of the Johnson & Johnson vaccine provides an efficacy of 76.7% after 14 days of administration of the first dose. However, a phase 3 trial showed an efficacy of 66.9% after 14 days and 66.1% after 28 days of vaccination. The efficacy of preventing severe infection was 76.7% after 14 days and 85.4% after 28 days which is quite high [46,47]. However, other studies reveal that it was 66% effective in preventing symptomatic COVID-19, 85% in severe COVID-19, and 100% in preventing hospitalization or death [48,49].
The virus mutations have resulted in variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617 (delta), and the newer omicron (B.1.1.7), which has enhanced transmissibility and fatality rates [50-52]. The S genes of B.1.351 and P.1 have various mutations and that might be the reason for re-infection by vanishing neutralizing antibodies formed during infection by the alpha variant [53,54]. The recent delta variant is characterized by spike protein mutations. P681R is at the S1-S2 cleavage site, and this variant has replication at its peak with higher transmissibility [55]. The first case of the recent omicron (B.1.1.529) with mutations in the RBD and NTD first emerged in South Africa in November 2021. The risk of reinfection is 5.4 times greater with omicron than that of the delta variant [56,57]. The emergence of these variants globally is illustrated in Figure 1.
The efficacy of single doses of BNT162b2 and ChAdOx1nCoV-19 vaccines against the delta variant is approximately 36% and 30%, respectively. However, the second dose increases the efficacy to 88% and 67%, respectively. A study from Scotland revealed that the efficacy of Covaxin is 81% against the alpha variant and 61% against the delta variant [58]. The efficacy of Covaxin against the delta variant is around 65% according to a phase 3 trial study [59]. The efficacy of Pfizer and AstraZeneca after the second dose was found to be 78% and 61%, respectively [60]. However, Pfizer-BioTech and Oxford-AstraZeneca vaccines were highly efficacious against delta variants but dropped over time [61]. Alpha variants have a 1.8-2-fold reduction in neutralizing antibodies of Moderna, Sputnik, and Novovax vaccines. The neutralizing capacity for the P.1 variant among vaccinated individuals was reduced by 6.7 for the Pfizer vaccine and 4.5 for the Moderna vaccine [62]. Delta variants have a 7-10 fold reduction in neutralizing antibody levels of Pfizer, Moderna, and Sputnik, and a 2-3-fold reduction in the case of Covishield and Covaxin; however, the sample study with Johnson and Johnson showed that it neutralizes the delta variant similar to Sputnik. However, Sputnik against B.1.351 variant showed a 6.1-fold reduction in neutralizing antibodies [63]. In another study, sera fromAstraZeneca recipients showed a 4.1-32.5-fold reduction in neutralizing activity against B.1.351 [64]. However, the reduction in the neutralizing antibodies in the sera of individuals receiving Moderna and BioNTech vaccines was 6.5-8.6-fold [62]. ZyCov-D is another DNA vaccine that is claimed to be effective against the delta variant in clinical trials [65]. The efficacy of these vaccines and the reduction in the neutralizing capacity of COVID-19 vaccines against variants of COVID-19 are presented in Table 1 and Table 2. Vaccinated people affected with the alpha variant had a lower viral load, whereas vaccinated individuals infected with the delta variant had a higher viral load. Thus, irrespective of the vaccine administered, the efficacy is reduced against the delta virus, but still effective in reducing fatality. Until October 2021, globally, 676 crore doses were given and 288 crore individuals were fully vaccinated, that is, 36.9% of the population. In India, 99.7 crore doses were administered to 29.2 crore individuals (21.1%) who are fully vaccinated [66]. The research is still ongoing regarding vaccine efficacy against omicron; however, researchers have found that two doses of the Pfizer vaccine provide 70% infection against hospitalization and 33% against infection [67]. As the efficacy wanes over time, researchers are insisting on having a third dose/booster dose which helps in boosting the efficacy. Recent studies have focused on the combination of booster doses for better efficacy. There was no increase in the efficacy against omicron even after the two doses of AstraZeneca, and this variant reduced the efficacy of Pfizer/Moderna to 10% even after two doses which increased to 40-50% and the effectiveness against hospitalization also increased to 88% after the booster dose [68]. The booster dose increases the neutralizing antibody titers by 25-fold with the Pfizer vaccine [69]. The recent study ofvaccineBNT162b2 among the pediatric population (5-11 years) showed 95% efficacy after two doses [70]. Because the efficacy of vaccines against the omicron variant is under investigation, the data available to date is presented in Table 3; however, this might change as studies are published.
A second line of defense the immune systems T cells may offer protection from COVID-19 even when vaccine-induced antibodies no longer can, according to new research out of the University of Wisconsin School of Veterinary Medicine.
The researchers discovered that a new, protein-based vaccine against the original version of the COVID-19 virus was able to teach mouse T cells how to recognize and kill cells infected with new, mutated versions of the virus. This T cell protection worked even when antibodies lost their ability to recognize and neutralize mutated SARS-CoV-2, the virus that causes COVID-19.
Marulasiddappa Suresh
Antibodies prevent COVID-19 infection, but if new variants escape these antibodies, T cells are there to provide a second line of protection, explains lead scientist Marulasiddappa Suresh, a professor of immunology and associate dean for research at the School of Veterinary Medicine.
The study, published in the Proceedings of the National Academy of Sciences on May 13, investigates the role of T cells, a specialized type of white blood cell, in defending against COVID-19 when antibodies fail.
When you receive a COVID-19 vaccine, your body learns to produce antibodies, proteins in the immune system that bind to and neutralize SARS-CoV-2. These antibodies circulate in the blood stream and protect you from illness by patrolling the nostrils, airways and lungs and wiping out the virus before it can cause infection or disease.
However, as SARS-CoV-2 mutates, these highly specific antibodies are less able to recognize new viral variants especially if the changes occur on the viruss spike protein, where the vaccines antibodies bind. This was especially apparent during the recent wave of the SARS-CoV-2 omicron variant, which has a staggering 37 mutations on its spike protein, making it more able to evade antibodies targeting the original viruss spike protein.
The biggest problem right now is that none of our current COVID-19 vaccines give complete protection against infection from emerging variants, especially the omicron sublineages BA.1 and BA.2, Suresh says.
Thats where T cells can help. Killer T cells aid the immune system by hunting and eliminating virus factories infected cells, says Suresh. So, when antibodies cannot neutralize the virus prior to infection, T cells can clear it quickly, causing mild or no noticeable symptoms.
With this information in hand, the UWMadison research team, co-led by Suresh and professor of pathobiological sciences Jorge Osorio and assisted by scientist Brock Kingstad-Bakke and doctoral student Woojong Lee, explored how T cells and antibodies can work to prevent COVID-19 infection altogether.
Brock Kingstad-Bakke, a scientist in the UW School of Veterinary Medicine. Photo courtesy of the School of Veterinary Medicine
The researchers developed an experimental protein-based vaccine containing the unmutated version of the spike protein from the original SARS-CoV-2 virus. This vaccine was also designed to elicit a strong T cell response to the viral spike protein, allowing the lab to test the extent to which T cells can protect against COVID-19 infection in the presence and absence of virus neutralizing antibodies.
After injecting mice models with their vaccine, researchers then exposed them to two SARS-CoV-2 variants and tested their susceptibility to infection under different conditions.
While vaccine-stimulated antibodies were unable to neutralize the mutated SARS-CoV-2 variants, mice were still immune to COVID-19 caused by the mutated viruses, due to action by T cells that were induced by the vaccine.
Unlike antibodies, T cells are able to detect unfamiliar strains of virus because the viral fragment that they recognize does not change considerably from one variant to the next.
This work has important implications for future T cell-based vaccines that could provide broad protection against emerging SARS-CoV-2 variants. The experimental vaccine is protein-based and designed to evoke a strong T cell response, differentiating it from currently available mRNA vaccines.
Now, the Suresh lab is studying how exactly T cells defend against SARS-CoV-2 and whether commercially available COVID-19 vaccines may induce these same mechanisms of T cell immunity to protect against emerging variants when the virus dodges established antibodies.
I see the next generation of vaccines being able to provide immunity to current and future COVID-19 variants by stimulating both broadly-neutralizing antibodies and T cell immunity, Suresh says.
This work was supported in part by the National Institutes of Health (grants U01 AI124299, R21 AI149793-01A1).
