Senate Bill 295, filed by Smithfield Senator Lindsey Tichenor, is being billed as a medical freedom measure.
In a statement, Tichenor argues Kentucky citizens were "forced to make compromising health decisions in order to retain their employment, gain access to medical treatment, or to enroll in schools during the response to the pandemic." The bill would block compulsory COVID or mRNA-based vaccinations in those instances.
The lawmaker goes on to call the vaccines "ineffective" and "dangerous."
SB 295 represents a pivotal step in addressing the complexities surrounding vaccination mandates and underscores the importance of preserving individual liberties in the face of public health challenges, Tichenor wrote.
The largest study to date of COVID vaccine safety looked at nearly 100 million vaccinated people across eight countries. The World Health Organization's Global Vaccine Data Network examined 13 medical conditions, including myocarditis, convulsion, and Guillain-Barr syndrome and found elevated risks associated with the vaccines.
Even with the findings, however, researchers concluded the risks from COVID-19 itself remain much higher than the risks of adverse events.
As the world navigates through the lingering mist of the COVID-19 pandemic, a groundbreaking study has emerged, casting a new light on the voyage we've embarked upon with mass vaccination. This exploration, encompassing the health data of approximately 46 million souls, reveals a compelling narrative about the vaccines designed to shield us from the virus's wrath. It's a tale of protection against severe illness and an unexpected champion of heart health, despite unveiling a slight uptick in certain medical conditions.
The study in question unfurls a tapestry of data illustrating that vaccines not only arm us against COVID-19 but also fortify our defenses against heart attacks, strokes, and other menacing blood clot-related conditions for a span extending at least six months post-administration. This revelation is particularly poignant, considering the virus itself can set the stage for serious cardiovascular complications. The essence of this discovery lies not merely in the numbers but in the lives potentially saved by this dual protection.
Yet, no journey is without its perils. The study acknowledges a slight increase in the risk of certain conditions, including Guillain-Barr syndrome, Bell's palsy, convulsions, myocarditis, and pericarditis, attributed to the vaccines from Moderna, Pfizer-BioNTech, and AstraZeneca. Myocarditis cases, for instance, showed a notable increase following the second dose of Moderna's vaccine. However, the narrative takes a turn when considering these adverse effects remain significantly rarer compared to the risks posed by the virus itself. The dialogue surrounding vaccine safety is nuanced, emphasizing that while the journey is not devoid of risk, the path of vaccination leads to a greater safeguard against the tempestuous seas of COVID-19.
In the wake of these findings, the medical community and public health officials remain steadfast in their support for vaccination. The Global COVID Vaccine Safety project, backed by esteemed institutions, steers this ship with a clear message: the benefits of COVID-19 vaccination far outweigh the potential risks. This stance is not born out of complacency but from a rigorous examination of the data at hand. As we venture further into this uncharted territory, the potential for refining vaccine formulations and administration strategies illuminates the horizon, promising smoother seas ahead for global health.
In essence, the study underscores the critical importance of vaccination in our collective battle against COVID-19. It serves as a reminder of the vaccines' role not just as a shield against the virus but as a beacon of hope for preventing the heart-related storms that the virus can provoke. As we continue to sail through these turbulent times, the key to navigating safely lies in heeding the science, understanding the risks, and embracing the protective embrace of vaccination.
(Precision Vaccinations News)
The US Food and Drug Administration (FDA) announced in a post on X that on May 16, 2024, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) will hold a public discussion to recommend the selection of strain(s) to be included in the 2024-2025 formula for COVID-19 vaccines.
On February 26, 2024, the FDA confirmed that changes to the vaccine composition may be necessary based on the currently circulating strains of the virus that causes COVID-19.
After receiving any recommendations from the VRBPAC regarding the 2024-2025 formula update, the FDA plans to take appropriate regulatory actions on updated COVID-19 vaccines so that manufacturers can make them available by September 2024.
The FDA expects that the composition of COVID-19 vaccines may need to be updated annually, as is done for seasonal influenza vaccines.
Background material and the link to the online teleconference and/or video conference meeting will be available on theAdvisory Committee calendar no later than twobusiness days before the VRBPAC meeting.
Oral presentations from the public will be scheduled between approximately 1 p.m. and 2 p.m. Eastern Time.
Contact Information:Sussan Paydar or Prabhakara Atreya, Center for Biologics Evaluation and Research, FDA, 202-657-8533 or[emailprotected].
Laura Santhanam:
You know, we've been dealing with misinformation for quite some time when it comes to vaccines. You know, it starting in in the late 1990s, with thinking about the measles, mumps rubella vaccine, and to this day, there are still people who, you know, withhold that vaccine from their children, because they think it might cause problems that just evidence studies conducted over so many years in so many countries. Just it they continue to debunk that since retracted study.
But that sort of laid the groundwork for some of the misinformation campaigns we're seeing about COVID vaccine now, whether it's talking about how quickly it was deployed, and then, you know, when politics are getting involved in some of those campaigns, it makes it a message disentangle.
Time and again, when I've been talking to clinicians about this, they recommend that people ask their doctors, if you have questions about the COVID vaccine, measles vaccine, any of these vaccines that are recommended that are approved and vetted by the CDC, by the FDA, you know, have those conversations with your doctors.
But also, you know, perhaps equally importantly, doctors should be ready to have those conversations with their patients. I had a conversation with a doctor in South Alabama who was saying, you know, physicians should be welcoming these conversations. They should be ready to answer questions, and shouldn't discourage patients from having them in the first place.
Vaccine misinformation expert also told me that people are going to misinformation for a number of reasons. But some of those reasons is because they weren't able to get answers when they needed them from their health care providers in the first place. So it just be ready to have these conversations and welcome them.
Thanks for joining us today and for your questions -- far more than we were able to address in a short space of time.
We hope youve found this discussion useful -- Covid-19 remains a controversial topic, but Michelle and I and the rest of Bloombergs healthcare team are using a data, fact-led approach.
Human Rights Act
The states supreme court found the vaccine rules for police were unlawful and those for paramedics were ineffective. Heres what the judgment means
Wed 28 Feb 2024 01.34 EST
The Queensland supreme court has thrown out the states Covid-19 vaccination mandate for paramedics and police, on the basis of the Human Rights Act.
Guardian Australia spoke to a range of human rights experts to understand the ramifications of Tuesdays decision.
What does the decision mean?
It means 74 named applicants to the court, who are current employees of the ambulance and police services, cannot be fired or otherwise disciplined as a result of not following the vaccine mandate.
What was the basis for the decision?
There were essentially two different reasons for the decision, depending on whether applicants worked for the police force or Queensland health.
Senior judge administrator Glenn Martin ruled that police commissioner, Katarina Carroll, didnt follow the right process under the Human Rights Act and failed to give proper consideration to human rights relevant to those decisions. As a result, those decisions were unlawful.
The courts decision was even more technical with regard to the ambulance service. That application succeeded because the health service was unable to provide sufficient evidence to show that the order was a power contained in an employment contract. The ambulance service order was not unlawful, just ineffective.
Griffith University human rights law professor Sarah Joseph described it as a procedural rather than substantive breach of the act, and a narrow decision.
Is the decision final?
Not necessarily. It could be appealed in the supreme court of appeal. Both Queensland health and the Queensland police said on Tuesday they were considering their legal options.
How did this happen in the first place?
The applicants challenged two decisions in 2021 and 2022 by the commissioner of police, and the then director general of Queensland health, Dr John Wakefield, that staff must be vaccinated against Covid-19 or else face disciplinary action or even sacking. Both mandates were quashed, in December 2022 and September 2023, respectively.
After a 21-month wait, a joint judgment was handed down on Tuesday at the Queensland supreme court. Its the first time a vaccine mandate has failed in court in Australia.
What does this mean for other states?
The decision is very narrow and based on the state Human Rights Act, which only applies in Queensland. It is also based entirely on the way Queensland decision-makers issued that specific mandate.
The only other state with a Human Rights Act is Victoria, which has a similar requirement for government to consider human rights when making decisions. The ACT also has a Human Rights Act.
Theoretically, lawyers in those jurisdictions could make out a similar case that their state decision-makers failed to consider human rights properly before imposing vaccination mandates.
Does it mean all vaccine mandates are illegal?
Definitely not.
In fact the court has explicitly ruled otherwise.
Queensland health has imposed all sorts of vaccine mandates on its staff for a very long time. Nurses, doctors, paramedics and even health volunteers have to be vaccinated against various diseases, ranging from tuberculosis to whooping cough, to keep their job. They still do and these rules are all still legal.
On Tuesday, the health minister, Shannon Fentiman, told media the decision did not affect the health directive imposed on the broader community of employees of Queensland health, including doctors and nurses, only employees of the ambulance service.
Martin was asked to rule that the mandate violated rights against discrimination, to equality before the law, against torture, to freedom of political thought and belief, to privacy, to life, to take part in public life and the right to liberty and security, among others. He ruled none of these rights were limited at all.
The only right that was impeded, he found, was the right not to be subjected to medical treatment without consent. Martin found public servants were coerced into vaccination because they feared loss of employment and income.
However, the states Human Rights Act does allow rights to be limited, the limits just need to be demonstrably reasonable.
Martin ruled that the restriction of that right was reasonable given the circumstances of the pandemic.
However, the act doesnt just require a decision-maker to come to the right decision they also have to do it the correct way, and document this process.
Some lawyers say if the police commissioner had done so, the court might have ruled a different way on the police element of the case.
Does it mean sacked police and paramedics can sue for compensation?
Billionaire businessman Clive Palmer who says he provided millions for the successful case said he would be happy to fund future legal action, potentially a class action lawsuit.
Lawyers for the police applicants also hinted at civil litigation in the future.
Human rights professor Sarah Joseph said she couldnt predict how compensation claims would play out, but said the chances of winning a litigation lawsuit against the government today are much bigger than they were yesterday.
Benedict Coyne, who acted for many of the police service employees in the case, said the case would have a significant impact on others outside the group of litigants, including officers who were sacked as a result of the mandates.
What does this mean for the state Human Rights Act?
Human rights advocates have celebrated the outcome.
In a state without an upper house, Queensland has often been said to have an accountability deficit in its government.
Its now clear the act is capable of acting as a check on the actions of governments.
Michael Cope, the president of the Queensland Council for Civil Liberties, said some elements of the judgment represented the first time sections of the Human Rights Act had been tested in the supreme court, blazing a precedent for future cases.
This is a reminder to everybody that that is the law in this state and if you dont do it, you can have your decision declared to be in breach of the Human Rights Act, Cope said.
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Anti-RBD IgG titers and plasma neutralizing activity induced by COVID-19 mRNA vaccination in HDs and LTRs
We enrolled 44 HDs and 54 LTRs to comprehensively evaluate mRNA vaccine-induced antibodies and cellular immune responses (Table1). The mRNA vaccines, Pfizer BNT162b2 or Moderna mRNA-1273 were investigated. Blood samples were obtained at five-time points: before vaccination, 1, 3, and 6 months after the second vaccination, and 1 month after the third vaccination (Fig.1a).
a Schematic overview of the cohort. b Anti-RBD IgG endpoint titers in HDs (black) and LTRs (red) (sample size, pre: 25 vs 12, 1m after 2nd: 25 vs 54, 3m after 2nd: 24 vs 53, 6m after 2nd: 44 vs 54, 1m after 3rd: 44 vs 51). c Multivariable logistic regression model (OR and 95% CI) for predictors of weak and strong responders (lower and higher than median antibody titer in HDs at 1 month after third vaccination, respectively). d Anti-RBD antibody titers in HDs (black), LTRs taking only a calcineurin inhibitor (CNI group, red) and LTRs taking CNI and other medications (CNI+other drug(s) group, blue) (sample size, pre: 25 vs 1 vs 11, 1m after 2nd: 25 vs 20 vs 27, 3m after 2nd: 25 vs 23 vs 30, 6m after 2nd: 44 vs 23 vs 31, 1m after 3rd: 44 vs 21 vs 29). e Anti-RBD IgG endpoint titers in HDs 1 month after 2nd vaccination (black) and in CNI+other drug(s) group 1 month after 3rd vaccination (blue) (sample size, 25 vs 29). f Fold-induction in anti-RBD IgG endpoint titers after third vaccination (HDs: black, CNI: red, CNI+other drug(s): blue). Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders. (sample size, 44 vs 21 vs 29). g pVNT50 against SARS-CoV-2 Wuhan-1 (HDs: black, CNI: red, CNI+other drug(s): blue). h pVNT50 in HDs 1 month after 2nd vaccination (black) and in CNI+other drug(s) group 1 month after 3rd vaccination (blue) (sample size, 25 vs 29). i Fold-induction in pVNT50 after third vaccination. Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders (HDs: black, CNI: red, CNI+other drug(s): blue) (sample size, 44 vs 21 vs 29). P values (two-sided) were calculated using the MannWhitney U-test. All experiments were performed once. Error bars indicate the interquartile range.
All LTRs were administered CNIs, such as tacrolimus or cyclosporine. Some LTRs took additional medications, such as the metabolic antagonist MMF, a steroid, or the mTOR inhibitor everolimus. Specifically, 23, 12, 2, 11, 5, and 1 LTRs had taken only a CNI; CNI and MMF; CNI and everolimus; CNI and a steroid; CNI, MMF, and a steroid; and CNI, everolimus, and a steroid, respectively. Seven LTRs received entecavir, a drug used to treat hepatitis B, and immunosuppressive therapy.
Anti-RBD antibody titers in LTRs were significantly lower than those in HDs at all time points (Fig.1b) (p<0.0001 at 1 and 3 months, p=0.0005 at 6 months after the second vaccination, p=0.0002 after the third vaccination). Anti-RBD antibody titers in all HDs exceeded the WHO standard (dashed line, 1000U/mL); however, 53.2% of LTRs had anti-RBD antibody titers below the WHO standard at 1 month after the second vaccination. However, anti-RBD antibody titers in 92.2% of the LTRs after the third vaccination exceeded the WHO standard, suggesting that effective immune responses can be achieved in immunosuppressed LTRs by the third vaccination.
Interestingly, the variability in antibody levels among LTRs was wide compared with that in HDs. Therefore, we aimed to identify the factors that affect the variability in antibody production in LTRs. LTRs that obtained anti-RBD antibody levels higher and lower than the median value of antibody titers in HDs after the third vaccination were categorized as strong and weak responders, respectively. We conducted a multiple logistic regression analysis with clinical parameters (Fig.1c), suggesting that taking multiple drugs decreased antibody levels (p=0.0048, OR=0.0285).
We regrouped LTRs for comparison between LTRs taking only a CNI and taking a CNI and more drugs (CNI+other drug(s)) (Fig.1d). There was no difference in the antibody titers between the CNI group and HDs after the third vaccination. Contrarily, antibody titers were significantly lower in the CNI+other drug(s) group than in the HDs and the CNI group (p<0.0001 among HDs vs. CNI+other drug(s), p<0.0001 among CNI vs. CNI+other drug(s)). However, the anti-RBD antibody titers after the third vaccination in the CNI+other drug(s) group were the same as those in HDs 1 month after the second vaccination (Fig.1e; p=0.3255). After the second vaccination, anti-RBD antibodies in plasma were induced in 49 of 54 LTRs. The 5 LTRs in whom anti-RBD antibodies were not induced after the second vaccination all showed induction of the antibodies after the third vaccination. However, there was one individual who, despite having a positive plasma anti-RBD antibody titer after the second dose, did not benefit from the third booster dose and tested negative. This individual was taking three medications, namely CNI, MMF, and steroids (5mg/day), and had a low anti-RBD antibody titer even after the second vaccination.
Additionally, LTRs were regrouped based on clinical information apart from medication (Supplementary Fig.1). Antibody titers were considerably lower in deceased donor liver transplant (DDLT) than in living-donor liver transplant (LDLT) (Supplementary Fig.1a). Furthermore, antibody titers in LTRs less than 12 years after transplantation were lower (Supplementary Fig.1b). LTRs who experienced rejection reactions after transplantation also exhibited lower antibody titers than those who did not (Supplementary Fig.1c). LTRs who have taken MMF also exhibited lower antibody titers than those who have not (Supplementary Fig.1d). These factors are related to the regimen of immunosuppressive drugs, and the multivariate analysis suggested that the number of drugs has the most significant impact. Noteworthily, antibody titers of 89.7% in the CNI+other drug(s) group were increased by the third vaccination, and the fold induction of antibody titers in the CNI+other drug(s) group was similar to that in HDs (Fig.1f; p=0.7666).
Next, we measured the changes in the neutralizing activity of plasma from HDs and LTRs (Fig.1g). Neutralizing activity in most of the CNI+other drug(s) was below the detection limit after the second vaccination, and was significantly lower than that in HDs after the third vaccination (p=0.0001). Contrarily, the neutralizing activity in the CNI+other drug(s) group after the third vaccination was similar to that in HDs one month after the second vaccination (Fig.1h; p=0.2985). Furthermore, although the fold-induction of neutralizing activity in CNI+other drug(s) by the third vaccination was significantly lower than that of HDs, 82.8% of the CNI+other drug(s) group got a booster effect (Fig.1i) (p=0.0006 among HDs vs. CNI+other drug(s)). These results suggest that the third doses of mRNA vaccine are worthwhile for the induction of neutralizing activity in LTRs, but may not be sufficient compared to HDs.
Generally, immunosuppressive drugs, including CNIs, contribute to the suppression of T-cell responses. To investigate whether the reduction in antibody titers in LTRs is affected by changes in CD4 helper T-cell function, we performed flow cytometry analysis to evaluate the CD4+ T-cell responses. The frequency of total SARS-CoV-2 spike-specific CD4+ Tcells was measured using CD154 as an activation marker (Supplementary Fig.2a). The frequency of spike-specific CD4+ Tcells in CNI+other drug(s) at 1, 3, and 6 months after the second vaccination was significantly lower compared to HDs (Fig.2a; p=0.0117, p=0.0208, and p=0.0047 at 1, 3, and 6 months after the second vaccination, respectively). There was no significant difference between HDs and the CNI group at 1 month (p>0.9999), 3 months (p=0.6506), and 6 months (p=0.1379) after the second vaccination. Moreover, there were significant differences between the CNI and CNI+other drug(s) groups 3 months (p=0.024), and 6 months (p=0.0051) after the second vaccination (Fig.2a). However, there is no significant difference among HDs, the CNI group, and the CNI+other drug(s) group after the third vaccination. Regardless of HDs or LTRs, spike-specific CD4+ Tcells decreased over time after the second mRNA vaccination (Supplementary Fig.2b).
Frequency of spike-specific CD154+ (a), Th1 (b), and Th2 (c) CD4+ Tcells in total memory Tcells from HDs (black), CNI group (red), and CNI+other drug(s) group (blue). df Fold-induction of spike-specific CD154+, Th1, and Th2 CD4+ Tcells by the third vaccination. Pie charts represent the proportion of individuals with fold-induction higher than 1, and gray slice shows frequency of negative responders. (HDs: black, CNI: red, CNI+other drug(s): blue). g The ratio of spike-specific Th1 to Th2 CD4+ Tcells (HDs: black, CNI: red, CNI+other drug(s): blue). P values (two-sided) in (a) to (g) were calculated using the Mann-Whitney U-test. h Correlation matrix of antibody and CD4+ T-cell responses in HDs and LTRs. Shades of blue represent positive correlations approaching 1, while shades of red denote negative correlations nearing -1. P values (two-sided) were calculated using the Spearmans rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.
Next, we measured the cytokine profiles of the total spike-specific CD4+ Tcells (Fig.2b, c, Supplementary Fig.2a). The frequency of Th1 cells in CNI+other drug(s) after the second vaccination was significantly lower compared to HDs (Fig.2b). On the contrary, the frequency of Th2 cells was higher in the CNI group than in HDs (Fig.2c). The frequency of total CD154+ spike-specific CD4+ Tcells and Th1 cells increased by the third mRNA vaccination in HDs and LTRs, and there was no significant difference between HDs and LTRs after the third vaccination (Fig.2a, b).
We next examined the effect of the third booster on memory CD4+ T cell responses by calculating the fold-induction of CD154+, Th1, and Th2 cell frequencies. We observed a boost effect in ~75% of individuals for CD154+ and Th1 cells in all groups, and in ~50% of individuals for Th2 cells (Fig.2df). Furthermore, Th1/Th2 ratio in LTRs was significantly lower compared to HDs (Fig.2g), suggesting that LTRs are more susceptible to the induction of Th2-biased CD4+ T-cell responses.
We next evaluated the correlation between CD4+ T-cell and antibody responses. One month after the second vaccination, the frequency of CD154+CD4+ T and Th1 cells was positively correlated with anti-RBD antibody titers in HDs and LTRs (Fig.2h). Moreover, CD4+ T-cell frequency before the third vaccination positively correlated with antibody titers after the third vaccination (HDs: r=0.299, p=0.049 for CD154+CD4+ Tcells vs. anti-RBD IgG; LTRs: r=0.483, p=0.0004 for CD154+CD4+ Tcells vs. anti-RBD IgG; r=0.433, p=0.0019 for Th1 CD4 Tcells vs. anti-RBD IgG). These results suggest that long-term CD4+ T-cell responses after the second vaccination contribute to the booster effect on antibody levels after the third vaccination.
In addition to antibodies and CD4+ Tcells, CD8+ T-cell responses also contribute to defense against SARS-CoV-2 infection22,23. However, COVID-19 mRNA vaccines reportedly have a lower ability to induce CD8+ Tcells than CD4+ Tcells24. Moreover, few reports demonstrate CD8+ T-cell responses to mRNA vaccines in LTRs. Therefore, we investigated whether spike-specific CD8+ Tcells were induced in LTRs and compared their frequency with HDs. We defined 4-1BB+CD69+CD8+ Tcells as spike-specific CD8+ Tcells in the PBMCs stimulated with spike peptides (Supplementary Fig.3a). Spike-specific CD8+ Tcells were detected in 100% of HDs and 93% of LTRs 1 month after the second vaccination (Fig.3a). However, the frequency of spike-specific CD8+ Tcells by the third vaccination did not increase in most HDs and LTRs (Fig.3b, HDs 55.8%, CNI 55%, and CNI+other drug(s) 42.9%). Compared to HDs, the frequency of LTRs was significantly lower at all time points, regardless of taking single or multiple drugs (Fig.3a). Furthermore, in contrast to antibody responses, there was no correlation between spike-specific CD8+ and CD4+ T cell responses (Fig.3c). These results suggest that the third boost effect on memory T-cell responses differs between CD4+ and CD8+ Tcells. We then checked the differentiation status of the spike-specific CD8+ T cells induced by vaccination using CD27, CD45RO, and CD57 markers to define central memory (CM; CD27+CD45RO+), effector memory (EM; CD27-CD57-), and effector (CD27-CD57+) subsets. As a result, the phenotypes of spike-specific CD8+ T cells were changed from CM to EM at 6 months after 2nd vaccination in both the HDs and LTRs who showed positive effects of boosting spike-specific CD8+ T-cell responses (Healthy boost+ and LTR boost+), although the phenotypes of total memory CD8+ T cells were not changed over time (Fig.3d, e). After 3rd mRNA vaccination, HDs and LTRs showed different phenotypes of spike-specific CD8+ T cells, with decreased CM and increased EM and Effector in HDs, but a trend toward increased CM in LTRs.
a Frequencies of spike-specific CD69+4-1BB+CD8+ Tcells in total memory Tcells from HDs (black), CNI group (red), and CNI+other drug(s) group (blue). b Fold-induction of spike-specific CD69+4-1BB+CD8+ Tcells after third vaccination. Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders (HDs: black, CNI: red, CNI+other drug(s): blue). c Correlation matrix of CD4+ and CD8+ T-cell responses. Shades of blue represent positive correlations approaching 1, while shades of red denote negative correlations nearing -1. P values were calculated using the Spearmans rank test. Frequencies of CM, EM and effector within CD8+ total memory T cells (d) and spike-specific CD69+4-1BB+CD8+ Tcells (e) in individuals who did (boost+) or did not (boost-) receive boost effect from 3 doses of mRNA vaccine (HDs boost: gray, HDs boost+: black, LTRs boost: red, LTRs boost+: dark red). P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test compared to 1 month after 2nd vaccination. Frequency of spike-specific CD69+4-1BB+CD8+ Tcells expressing GZMA (f), GZMB (g), and Perforin (h) (HDs: black, CNI: red, CNI+other drug(s): blue). i Expression of multiple cytotoxic molecules in spike-specific CD69+4-1BB+CD8+ Tcells. Each colors arc length and pie charts area represent the expression of each cytotoxic molecule (GZMA: red, GZMB: blue, Perforin: green) and cells expressing the indicated number of cytotoxic molecules (0: yellow, 1: green, 2: blue, 3: red), respectively. P values (two-sided) in (a), (b), (f), (g), and (h) were calculated using the MannWhitney U-test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.
Furthermore, we previously reported that differences in the expression patterns of cytotoxic molecules could observe qualitative differences in mRNA vaccine-induced spike-specific CD8+ Tcells20. Therefore, we compared the expression of cytotoxic molecules in spike-specific CD8+ Tcells between HDs and LTRs. Supplementary Fig.3b shows the expression patterns of GZMA, GZMB, and Perforin, and gating. Regardless of HDs or LTRs, most spike-specific CD8+ Tcells expressed GZMA before and after the third vaccination (Fig.3f). The proportion of cells expressing GZMA in CNI+other drug(s) was significantly, but slightly, lower than that in HDs before the third vaccination (p=0.0237). However, the proportion of cells expressing GZMB and Perforin was not different between HDs and LTRs before and after the third boost (Fig.3g, h). Furthermore, the expression profiles of GZMA, GZMB, and Perforin were not significantly different between the groups (Supplementary Fig.4a, b). The proportion of subpopulations expressing GZMA, GZMB, and Perforin was approximately 20% in the spike-specific CD8+ Tcells of each group, and the proportion of subpopulations expressing only GZMA was over 50% (Fig.3i). However, we did not observe any qualitative differences in spike-specific CD8+ Tcells induced by the third boost.
HDs and LTRs were vaccinated with an mRNA vaccine based on the Wuhan-1 strain, and the induced antibodies potentially reduced the effectiveness against the recently emerged Omicron sublineages. Therefore, we measured the antibody titers before and after the third boost against RBD corresponding to the Omicron sublineages, and found that anti-RBD antibody titers before the third boost against all sublineages were significantly reduced compared to those against the Wuhan-1 (Fig.4a, b). Among sublineages, the anti-RBD antibody titers against BQ.1.1 and XBB were particularly reduced (HDs, 8.43-fold reduction; CNI, 5.23-fold reduction; CNI+other drug(s), 4.41-fold reduction against BQ.1.1, HDs, 11.9-fold reduction; CNI, 6.35-fold reduction; CNI+other drug(s), 4.41-fold reduction against XBB). Furthermore, the neutralizing activity before the third boost was below the detection limit for BA.5, BQ.1.1, and XBB in most individuals (Fig.4c). Furthermore, there was no change in the trend toward lower antibody titers for each Omicron sublineage (Fig.4d, e). In particular, the CNI+other drug(s) group showed significantly lower anti-RBD antibody levels against all sublineages than the HDs and CNI groups. Additionally, there was a slight improvement in neutralizing activity against the BA.5 strain, but not BQ.1.1 and XBB strains, by the third vaccination (Fig.4f).
a, d Anti-RBD antibody endpoint titers against indicated strains at (a) pre- and (d) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). Fold-change of anti-RBD IgG against variants of concern endpoint titers at (b) pre- and (e) post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of red indicate a decrease in antibody titers, with darker shades signifying a larger negative fold change. pVNT50 against strains at (c) pre- and (f) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). P values (two-sided) in (a), (c), (d), and (f) were calculated using the MannWhitney U-test. P values (two-sided) in (b) and (e) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, pre-3rd boost: 44 vs 23 vs 31, post-3rd boost: 44 vs 21 vs 30). All experiments were performed once. Error bars indicate the interquartile range.
Collectively, these results suggest that the third vaccination with the Wuhan-1 mRNA vaccine may not be sufficient to induce antibody responses against Omicron sublineages, particularly BQ.1.1 and XBB, in HDs and LTRs.
Finally, we investigated the differences in cellular immunity against Omicron sublineages between HDs and LTRs. The frequency of spike-specific CD154+CD4+ Tcells was evaluated in PBMCs before the third boost. There was no difference in response to the Wuhan-1 and mutant strains in all groups (Supplementary Fig.5a, b). The same trend was observed for spike-specific Th1 CD4+ Tcells (Fig.5a, b). However, the frequency of CD154+CD4+ Tcells and Th1 cells responding to mutant strains in HDs after the third boost was significantly and slightly lower than that of cells responding to Wuhan-1(Supplementary Fig.5c, d, Fig.5c, d). The same trend was observed in spike-specific Th2 CD4+ Tcells (Supplementary Fig.4eh). These results indicate that, unlike antibody responses, CD4+ T-cell responses induced by mRNA vaccines can react to Omicron sublineages. Moreover, LTRs resulted in CD4+ T-cell responses to Omicron sublineages with comparable reactivity to those in HDs.
a Comparison of spike-specific Th1 CD4+ T-cell frequency against spike peptides in CD4+ total memory Tcells at pre-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). b Fold-change of spike-specific Th1 CD4+ T-cell frequency against variants of concern at pre-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. c Comparison of spike-specific Th1 CD4+ T-cell frequency against spike peptides in CD4+ total memory Tcells at post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). d Fold-change of spike-specific Th1 CD4+ T-cell frequency against variants of concern at post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.
Next, we investigated CD8+ T cell responses to Omicron sublineages. Interestingly, the frequency of spike-specific CD8+ T-cell responses to mutant strains was not significantly decreased, regardless of the pre- and post-third boost (Fig.6a, b). The fold-changes in the frequency of CD8+ T-cell responses to mutant strains relative to Wuhan-1 are shown (Fig.6c, d). Collectively, these results demonstrate that mRNA vaccines induce CD8+ T-cell responses reactive to BA.5, BQ.1.1, and XBB mutant strains and that these responses are maintained in LTRs.
Comparison of spike-specific CD69+4-1BB+ CD8+ T-cell frequency against spike peptides in CD8+ total memory Tcells at (a) pre- and (b) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). Fold-change of spike-specific CD8+ T-cell frequency against variants of concern at (c) pre- and (d) post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.
For Evans Jutta Kofi Attivor, each dot on the Google map represents an opportunity.
As Municipal Director of Health Service for Nkwanta South municipality of Ghana, Evans is working on catching up children who missed routine immunization during the COVID-19 pandemic in the Nkwanta South of Oti region, located in northeast Ghana. "Each dot represents the geolocation of a child who has missed vaccination, and was followed up through defaulter-tracing," he says.
Last summer, Evans joined the second cohort of theCOVID-19 Recovery for Routine Immunization Programs Fellowshipoffered by the Sabin Vaccine Institute and the World Health Organization. He attended Phase I of the Fellowship, a five-week live engagement series, and then submitted a strategic proposal on his project,Reducing missed opportunities for vaccination: A COVID-19 immunization recovery project in four sub-municipalities in Nkwanta South.
He was accepted to become one of the 60 individual or team Fellows chosen for Phase II, the mentorship program of the Fellowship. Supported with micro-grant funding to help bring his vaccination project to life, Evans and his team are using Google maps in the first round of the immunization project in the rural region.
He started the recovery effort in late 2023, with 12 Community Health Planning and Services (CHPS) facilities from four sub-municipalities out of 30 total. He hopes the project will eventually involve all 30, and possibly become a regional and even a national immunization tracking effort. "We have supervisors, unit heads and sub-municipal leaders from the four implementing sub-municipalities at monthly joint meetings, so all are aware of what's going on and we can reproduce these activities later," he says.
To start, the team focused on planning, partner development and resource mobilization, making certain that every facility had all supplies necessary, assuring that the cold chain structure was in place, and training completed for health care workers. Since 2020, his team has been using an immunization follow-up tool called Nkwanta South Municipal Home Visit/Follow-up Reporting Tool that was designed and deployed on the KoboCollect app. For the Fellowship project, a new app was designed to aid monitoring and data collection, which all supervisors downloaded onto their phones to help capture real-time data in the field. This new tool is designed to record vaccination dates and services provided during supervision as well as to make reporting by the supervisors easy and convenient. "It's part of making certain that we get valid reports," says Evans.
Evans Attivor
"The catch-up campaign includes both static (facility-based) and outreach activities," he adds. "We want to be able to compare our numbers from the field with what the facilities submit and make certain that we can follow up on any discrepancies, to find out exactly what happened and address them."
The main strategy they are using, defaulter tracing, allows the various teams to identify missed children per the vaccination records in the Nutrition and Child Health Registers. In one CHPS zone, the project successfully traced and immunized 81.4% of missed children. Those missed were due to Ill health, vaccine not opened to avoid wastage and child vaccinated but not recorded. Reasons why children defaulted initially included that the child was not available when the vaccination team visited, the shortage of vaccine and breakdown of the motorbike used to transport vaccines. "We work in difficult terrain," he says.
Attivor notes that some of the challenges to service delivery have included transportation and competing activities that sometimes interfere with field work. "We are, however, finding ways to execute all planned activities as well as track our progress," he added.
Midway through the implementation of his Fellowship project, five (41.7%) of the facilities have achieved or exceeded their goals and another four (33.3%) are making good progress. For the three outliers, "We know this is within our reach. We will revisit the data and liaise with the national and regional office to resolve the challenges."
As part of the Fellowship, Evans has been able to check in monthly with his mentor, Katrina Kretsinger, a global immunization expert from WHO. "The monthly meeting with my mentor, which I refer to as the M4 activity Mentee-Mentor Monthly Meeting has given me the chance to discuss opportunities and innovative ideas. I must say that Katrina has really provided me [with] technical advice, motivation and guidance."
Supervisors and facility in-charges after monthly review meeting held on Feb 19, 2024
Evans notes the commitment of his team of municipal and sub-municipal supervisors and the facility in-charges to continue tracing all missed children through home visits. They are also planning to continue conducting monthly reviews, data validation meetings and follow-up to address all issues of population discrepancy.
The Fellowship project, with its monthly group check-ins, training and results, has had a positive impact on everyone, says Evans. "The team is so excited about this project, and some say they are learning so much from it."
This article was originally published by the Sabin Vaccine Institute on 21 February 2024.
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A research team at Freie Universitt Berlin has conducted a comprehensive comparison of the efficacy of a mucosal, replication-competent but fully attenuated virus vaccine, sCPD9-FCS, with the monovalent mRNA vaccine BNT162b2 in preventing the transmission of SARS-CoV-2 variants.
The study, titled "An Intranasal Live-Attenuated SARS-CoV-2 Vaccine Limits Virus Transmission," is published in Nature Communications. The research addresses a critical challenge facing current vaccination strategiesnamely, the limited ability of intramuscularly administered vaccines to induce robust mucosal immune responses in the upper respiratory tract, the primary site of infection and virus shedding.
The researchers compared the efficacy of the live attenuated vaccine (LAV) sCPD9-FCS and a monovalent mRNA vaccine in preventing the spread of two SARS-CoV-2 variants: the ancestral B.1 and the omicron BA.5 in Syrian hamsters. They investigated the performance of the vaccines in two different scenarios.
In the first scenario, they evaluated the protective efficacy of the two vaccines by exposing vaccinated Syrian hamsters to infected antagonists. Here, the LAV vaccine completely blocked infection, while the mRNA vaccine offered no significant protection against infection.
In the second scenario, the transmission of the challenge virus from vaccinated and subsequently infected hamsters to unsuspecting contacts was investigated. In this scenario, transmission was blocked or strongly suppressed by the LAV vaccine but not by the mRNA vaccine. These results clearly showed that the LAV sCPD9-FCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios.
Freie Universitt Berlin virologist Dr. Jakob Trimpert, one of the lead authors of the study, said, "Our results provide compelling evidence for the benefits of locally administered live attenuated vaccines over intramuscularly administered mRNA vaccines. This is a significant advance in improving our ability to prevent infection and reduce virus transmission, particularly in the context of emerging SARS-CoV-2 variants."
According to the team, the COVID-19 pandemic has posed unprecedented challenges to research and society, and the continued spread of SARS-CoV-2 underscores the need for innovative vaccination strategies. The LAV sCPD9-FCS, which was developed by de-optimizing codon pairs, offers a promising solution as it induces strong mucosal immunity in the respiratory tract and systemic immunity against a range of SARS-CoV-2 antigens.
"Our study has addressed the shortcomings of existing vaccines and underscored the potential of intranasally administered vaccines to create a more effective barrier against infection, prevent virus replication and attenuate transmission," said Dr. Dusan Kunec, research group leader at the Institute of Virology at Freie Universitt Berlin, co-author and lead researcher of the study.
Rocketvax founders Dr. Vladimir and Dr. Natasa Cmiljanovic said, "The impressive preclinical results consistently confirm the advantages of our lead SARS-CoV-2 live vaccine candidate sCPD9-FCS, administered intranasally, over intramuscularly administered mRNA vaccines, prompting us to accelerate its further development and translation into clinical settings for its further validation."
According to the research team, the results of the study have significant implications for the future of COVID-19 vaccination strategies. The superiority of sCPD9-FCS in preventing transmission points to a promising avenue for further research and development of intranasal vaccines that offer a potential solution to the challenges posed by emerging variants.
This study provides compelling evidence for the superiority of the intranasally administered live attenuated vaccine sCPD9-FCS in preventing SARS-CoV-2 transmission. The study underscores the importance of exploring alternative vaccination approaches to address the evolving landscape of the COVID-19 pandemic.
More information: Julia M. Adler et al, An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission, Nature Communications (2024). DOI: 10.1038/s41467-024-45348-2
Journal information: Nature Communications
After four years of the first covid-19 case in Brazil, it isnt still possible to identify a pattern for the diseases behavior. With vaccination, the infection and death rates dwindled dramatically, as well as the seriousness of the disease for most of the population.
Continua aps publicidade
Even so, the high rate of transmissibility of the virus and the unpredictability of mutations impose a kind of "precarious equilibrium" on the current epidemiological situation.
Antonio Augusto Moura da Silva, an epidemiologist and professor of the Graduate Program in Collective Health at the Federal University of Maranho (UFMA, in Portuguese), states that, as the population acquires immunity against the virus, a pandemic may evolve to an endemic, that is, when a disease becomes recurring in a region, but without a significant number of cases or deaths.
The question that emerges is whether we have already reached this balance, that is, whether the situation has evolved into what we call an endemic. Currently, its difficult to determine whether or not it was reached. We cant affirm it. However, every state of equilibrium for all infectious diseases is always very fragile and can be disrupted by anything new," says the professor.
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Moura da Silva says that, although Brazil has not reached this stage, evidence indicates the country is walking "in this direction. However, any balance is precarious, especially if the virus develops a more aggressive mutation. A lethal mutation is a possibility. Mutations are random events, and we can't predict which way they will go," he explains.
This analysis has the same conclusion as Paulo Lotufo, a professor of Internal Medicine at the University of So Paulo Medical School, to whom there isnt yet a total comprehension of the diseases behavior.
He believes that, when dealing with the peaks of COVID-19 cases, its interesting to compare them to those of influenza. While the influenza season follows a well-defined time pattern, COVID still did not show this clarity, making it difficult to predict how things will develop. The vaccine, although its contribution to decreasing serious cases and deaths, doesnt provide for a broad comprehension of covid-19 peaks of cases, he states.
The current perception is that, as seen in other diseases, there will be more vulnerable individuals, such as those with heat conditions. This dynamic is similar to that of influenza, but the pandemic continues to uncover particularities yet to be totally understood and recorded given the complexity constantly evolving.
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In this sense, the continuous collection and recording of data is crucial due to the constant transformations, contributing to a more complete and efficient understanding in the management of the health system.
Isaac Schrarstzhaupt, an epidemiologist and data scientist at the Rede Anlise Covid (Covid Analysis Network, in English), also agrees that there is no pattern to the virus's behavior. He affirms further: he doesnt know whether it will be possible to identify some pattern due to the virus's high transmissibility.
Schrarstzhaupt says the SARS-CoV-2 is so infectious that it doesnt depend, for instance, on the seasons, which happens to flu during the winter, when people crowd indoors. In Covid's case, its more related to peoples behavior.
For instance, with people adopting prevention measures less frequently, such as the use of protective face masks, there is an increase in the rate of infection, regardless of whether it is winter or summer. As a result, there is a greater chance of the virus mutating and breaking the current control over the disease. "Mutation is a consequence of this high transmission rate because the virus enters the body, enters cells, begins to replicate, and then mutation occurs. A mutation can make the virus completely useless, or smarter. And then it becomes a new predominant variant."
It is mainly through this explanation that Schrarstzhaupt can't see the establishment of a pattern for the diseases behavior. "For this to happen, the virus would have to lose the capacity to mutate and create so many variants, and the predominant variant that remains would have to be more or less predictable, like influenza. SARS-CoV-2's high mutation rate is what makes me believe its unpredictable, at least not in the medium term," says the data.
Vaccination
In addition to being highly infectious, there is a low COVID-19 vaccination rate, especially among children. Researchers emphasize that the current epidemiological situation is significantly different from the scenario seen before the vaccine. Even so, adherence to the latest doses of the vaccine is lower than desired.
According to the Ministry of Health, from the beginning of COVID-19 vaccination in Brazil, on January 17, 2021, until February 6, 2024, 517 million doses were administered to the general public, 6.7 million of which were to children under five years of age.
Up until now, only 6% of children aged between six months and two years and 6.4% of children aged between three and four years have concluded the monovalent vaccination schedule (bivalent coverage is only for children aged 12 and over). The percentage is well below the target of 90% immunization coverage.
"To reduce cases, the population must adopt protective measures. However, to reduce serious cases and deaths, it's only through vaccination. Data show that the pandemic is nowhere near the emergency phase, but it is still serious and responsible for a large percentage of serious respiratory cases," especially among children and the elderly, says the data researcher.
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In 2024, up to the sixth epidemiological week (February 10-16), there were 4,937 hospitalized cases of Severe Acute Respiratory Syndrome (SARS), with 41% (2,020) of them identified as respiratory viruses. Of these, 64% were due to COVID-19. Regarding deaths, 506 SARS deaths were reported in the same period, with 56% (283) identified as respiratory viruses. Of these, 91% were due to COVID-19. The data is from the Ministry of Health's latest Epidemiological Bulletin.
The Ministry's data shows that the elderly are more infected than children. In terms of deaths, the elderly lead.
What does the Ministry of Health say?
Ethel Maciel, Secretary of Health and Environmental Surveillance at Brazils Ministry of Health, says the current epidemiological situation is "very different" from when the pandemic was considered a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). "After vaccination, there was very significant control of the disease. So we've gone from 3,000 people dying a day to an average of between 30 and 50 people a day," she explained.
This year, the COVID-19 vaccine became part of the countrys National Immunization Program (PNI, in Portuguese). The Ministry of Health's priority is children aged between six months and five years old and groups with a higher risk of developing severe forms of the disease: the elderly, immunocompromised people, pregnant and postpartum women, health workers, people with comorbidities, Indigenous people, river dwellers and quilombola people; people in long-term care institutions and their workers, people with permanent disabilities, people deprived of their liberty, teens and young people serving socio-educational measures, workers of the prison system, and people living on the streets.
The secretary highlights that "new strains may emerge. However, in the current scenario where the Omicron and its subvariants dominate our vaccines still protect. Our concern lies with those who are falling seriously ill and dying, which are mainly children under the age of two and adults over 70. Therefore, these groups are our current major concern."
"We've already seen a reduction in the number of deaths. Since we have a vaccine and medication, we don't want anyone to die. So one death is already a bad result. But we won't be able to eliminate it overnight. And we never can. We'll always have some remnants. But we're going to work towards an even greater reduction," says Maciel.
Edited by: Rodrigo Duro Coelho
