The Centers for Disease Control and Prevention is considering whether to recommend yet another Covid booster shot this spring, especially for people most at risk for severe complications of the illness.
A spring booster would be the same vaccine that was approved last fall, which was formulated to target the XBB.1.5 subvariant. The vaccine is also very effective against the JN.1 subvariant, which is causing almost all Covid infections in the U.S. right now.
While it's unlikely that the majority of Americans would opt for another dose just 21.9% of adults received the latest version of the vaccine experts say that it's critical to make it available sooner rather than later.
"Waiting till the fall, I think, is a mistake," said Michael Osterholm, an infectious disease expert and director of the Center for Infectious Disease Research and Policy at the University of Minnesota. "We have clear evidence that either vaccine or previous infection probably gives four to six months of relative protection against serious illness, hospitalizations and deaths, but wanes substantially after that."
Earlier this week, the CDC said it had no immediate plans to pull back on isolation guidelines for people who test positive for Covid.
Advisers to the CDC are expected to vote on whether to recommend a spring Covid booster during a meeting scheduled for Feb. 28, according to a source close to the Advisory Committee on Immunization Practices. It's expected that the panel will focus its discussion on those most vulnerable to Covid, including people age 65 and older and anyone with a weakened immune system, such as organ transplant recipients.
"The discussion will be aimed at the people who are most accepting of public health recommendations," said Dr. William Schaffner, an infectious diseases expert at Vanderbilt University Medical Center in Nashville, Tennessee. "The committee, in its rigorous fashion since the question has come up, will be considering a second dose for people at high risk or for people who wish to get it."
But even some vulnerable groups who usually adhere closely to their doctors' advice to get vaccinations are experiencing vaccine fatigue, said Dr. William Werbel, associate director of epidemiology and quantitative sciences with the Johns Hopkins Transplant Research Center in Baltimore.
"Some people have had seven, eight vaccines," Werbel said. "Transplant recipients would be more receptive and much more likely to follow recommendations, particularly if recommended by the transplant center, but the ceiling is kind of lowered because of this societal fatigue and societal disenchantment with Covid."
He added that he would recommend a spring booster to his patients if the CDC signs off on one.
Experts generally recommend waiting at least two months after a Covid vaccine or Covid infection before getting another shot, even for high-risk patients.
Vaccination rates are higher for people age 65 and older, at 42%, according to the CDC. Research shows that people who got the latest booster shot were 54% less likely to be infected with Covid this winter. That level of protection held against the strain found in nearly all circulation of Covid right now: JN.1.
The CDC is not required tofollow the advice of its advisory panels, but it usually does.
As of this month, emergency room visits, hospitalizations and deaths from Covid are down, according tothe latest CDC data.
"We're lucky that the vaccines are safe," Werbel said, "certainly much safer than getting Covid."
Erika Edwards is a health and medical news writer and reporter for NBC News and "TODAY."
In a surprise announcement, Russian President Vladimir Putin revealed a promising breakthrough in cancer research during a technology forum in Moscow.
Putin said that Russian scientists are on the verge of creating vaccines for cancer. He emphasized that these breakthrough vaccines would soon be accessible to patients, marking a potential turning point in the fight against cancer.
The Russian President's announcement, reported by Reuters, sheds light on the development of what he referred to as "cancer vaccines" and "immunomodulatory drugs of a new generation."
Despite the progress in cancer vaccine development worldwide, challenges persist in the realm of vaccine safety and efficacy.
President Vladimir Putin said on Wednesday that Russian scientists were close to creating vaccines for cancer that could soon be available to patients.
Mr. Putin said in televised comments that "we have come very close to the creation of so-called cancer vaccines and immunomodulatory drugs of a new generation".
"I hope that soon they will be effectively used as methods of individual therapy," he added, speaking at a Moscow forum on future technologies.
Mr. Putin did not specify which types of cancer the proposed vaccines would target, nor how.
A number of countries and companies are working on cancer vaccines. Last year the U.K. government signed an agreement with Germany-based BioNTech to launch clinical trials providing "personalised cancer treatments", aiming to reach 10,000 patients by 2030.
Pharmaceutical companies Moderna and Merck & Co are developing an experimental cancer vaccine that a mid-stage study showed cut the chance of recurrence or death from melanoma - the most deadly skin cancer - by half after three years of treatment.
There are currently six licensed vaccines against human papillomaviruses (HPV) that cause many cancers, including cervical cancer, according to the World Health Organization, as well as vaccines against hepatitis B (HBV), which can lead to liver cancer.
During the coronavirus pandemic, Russia developed its own Sputnik V vaccine against COVID-19 and sold it to a number of countries, although domestically it ran up against widespread public reluctance to get vaccinated.
Putin himself said he had taken Sputnik, in a bid to assure people of its efficacy and safety.
Women who are vaccinated against COVID-19 during pregnancy provide their infants with protection against the coronavirus for at least six months after birth the point when babies are eligible to get vaccinated themselves, new research shows.
No COVID-19 vaccine for infants under 6 months currently exists, making that population particularly vulnerable.But researchers have found that women who received mRNA-based COVID vaccinations or boosters during pregnancy provide enough protection to bridge that gap.
During an earlier leg of the study by the National Institute of Allergy and Infectious Diseases, pregnant volunteers were vaccinated against COVID. Antibodies induced by the vaccine could be found in their infants' cord blood, suggesting that they had some protection against the virus but researchers did not know how much or for how long.
The new results, published in the journal of the American Academy of Pediatrics,reinforce the importance of getting vaccinated during pregnancy andmay be comforting to families who employ outside caregivers or use daycare for their newborns and young infants.
Researchers analyzed data from 475 infants born while their pregnant mothers were enrolled in a COVID-19 vaccine study. The babies were evaluated at least once during their first six months of life, and parents reported whether their infants became infected with COVID-19 or developed symptoms.
The infants of mothers who received two COVID vaccine doses had a "robust antibody response at birth," while those born to mothers who had received an additional booster dose during pregnancy had higher levels of antibodies at birth and even more protection from COVID at follow-up visits. None of the infants involved in the study were hospitalized for COVID.
Researchers will continue to evaluate data from this study to glean further insights into COVID in infants.
The U.S. Centers for Disease Control and Prevention updated its guidelines in 2022 to recommend that children 6 months to 5 years old should receive COVID vaccines, but that still excluded newborns and young infants.
The National Institute of Allergy and Infectious Diseases is part of the National Institutes of Health.
Feb 15, 2024 12:31 pm EST
HOBOKEN, NJ The city of Hoboken is offering a host of health screenings, tests, and events in the next few weeks. Some are for seniors and some are for everyone.
The Hoboken Health Division and Hudson Regional Health Commission (HRHC) are hosting a COVID-19 and flu vaccine pop-up clinic on Feb. 15 from 3 p.m. to 7 p.m. at the Multi-Service Center, 124 Grand St. Appointments can be made at: https://www.hudsoncovidvax.org.
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In partnership with Save Latin America, $25 gift cards to Walmart or ShopRite will be given to vaccine recipients, while supplies last.
For eligibility and other information call (201) 420-2375.
COVID And Vaccine Stats, And Effects
Health officials recommend talking to your physician to decide whether the vaccine is right for you. You can see the current federal COVID vaccine recommendations, risks, and side effect reports here.
In New Jersey, 584 people are currently hospitalized with COVID, 34 of those on ventilators to help them breathe.
In April of 2020, at the height of the pandemic, approximately 6,000 people were hospitalized who were positive for COVID, with 1,277 on ventilators.
Free Covid Test Kits Available
Residents can pick up free COVID-19 testing kits, while supplies last, on Thursdays from 1 p.m. to 3 p.m., and Fridays from 10 a.m. to 12:30 p.m. through the end of this month at the Multi-Service Center, 124 Grand St. For more Information call (201) 420-2375.
Watch Patch for other upcoming free health events.
WASHINGTON (NEXSTAR) The coronavirus pandemic has caused many Americans to worry about side effects from vaccines. Rep. Marjorie Taylor Greene (R-Ga.) says shes heard horror stories.
All kinds of injuries, miscarriages, heart attacks, myocarditis, permanent disabilities, neurological problems, Greene said.
Talk like that makes Rep. Robert Garcia (D-Calif.) angry.
Its shameful that members of Congress continue to put down vaccinations as an opportunity to get our communities healthier, Garcia said.
Rep. Brad Wenstrup insists, the vaccines were effective and safe, and the real problem is communication.
Public perception becomes reality. And because of that, words matter, Wenstrup said. So, now we have a society that thinks that the polio vaccine and the other vaccines arent necessarily safe and effective.
Experts with the FDA agree it is necessary to reassure the public of the safety of vaccines and ensure their effectiveness.
If we want to maintain confidence in the vaccines and the other medical products that we authorize or approve, we must have very robust safety surveillance systems in place, Peter Marks, FDA Center for Biologics Evaluation and Research Director said.
Rep. Jamie Raskin (D-Md.) says the CDC and FDA need to avoid mistakes and shut down misinformation to save more lives.
Public health response of the federal government makes a huge difference in terms of health outcomes for the American people, Raskin said.
WASHINGTON (NEXSTAR) The coronavirus pandemic has caused many Americans to worry about side effects from vaccines. Rep. Marjorie Taylor Greene (R-Ga.) says shes heard horror stories.
All kinds of injuries, miscarriages, heart attacks, myocarditis, permanent disabilities, neurological problems, Greene said.
Talk like that makes Rep. Robert Garcia (D-Calif.) angry.
Its shameful that members of Congress continue to put down vaccinations as an opportunity to get our communities healthier, Garcia said.
Rep. Brad Wenstrup insists, the vaccines were effective and safe, and the real problem is communication.
Public perception becomes reality. And because of that, words matter, Wenstrup said. So, now we have a society that thinks that the polio vaccine and the other vaccines arent necessarily safe and effective.
Experts with the FDA agree it is necessary to reassure the public of the safety of vaccines and ensure their effectiveness.
If we want to maintain confidence in the vaccines and the other medical products that we authorize or approve, we must have very robust safety surveillance systems in place, Peter Marks, FDA Center for Biologics Evaluation and Research Director said.
Rep. Jamie Raskin (D-Md.) says the CDC and FDA need to avoid mistakes and shut down misinformation to save more lives.
Public health response of the federal government makes a huge difference in terms of health outcomes for the American people, Raskin said.
BOSTON and LEXINGTON, Mass., Feb. 15, 2024 /PRNewswire/ --The Defense Threat Reduction Agency's (DTRA) Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense (CBD) Program has awarded, through the Medical CBRN [Chemical, Biological, Radiological, and Nuclear] Defense Consortium (MCDC) requirement 22-05, "Adjuvant Activity to Vaccines Prototype," a 5-year contract totaling up to $31 million including program options to the team of Ginkgo Bioworks, Inc. (NYSE: DNA) and SaponiQx, Inc. (a subsidiary of Agenus Inc., NASDAQ:AGEN) to discover and develop next-generation vaccine adjuvants. Partners in adjuvant discovery and development since 2021, Ginkgo, which is building the leading platform for cell programming and biosecurity, and SaponiQx, developing a visionary adjuvant development platform, will use a combination of high-throughput empirical and artificial intelligence/machine learning approaches, including Generative Molecular Design (GMD), to develop superior novel saponin-based adjuvants.
Adjuvants are components of vaccines that help to enhance the magnitude, breadth, and duration of the immune response to vaccination. Currently, only a handful of adjuvants are available for human use in licensed vaccines. SaponiQx's STIMULON QS-21 is a key adjuvant component in market-leading vaccines for shingles, malaria, and respiratory syncytial virus. Novel adjuvants with enhanced properties, including tailored humoral and cellular immune responses, could pave the way for a new wave of innovative vaccines against existing and emerging pathogens.
"The COVID-19 pandemic revealed the critical need for safe, effective, and accessible vaccines against emerging biothreat agents," said Jennifer Wipf, SVP, Head of Commercial Cell Engineering at Ginkgo Bioworks. "Imagine a future where vaccines are not only more affordable but also provide consistent protection in fewer doses, without causing discomfort or requiring refrigeration. We're very excited by this opportunity to strengthen and expand the SaponiQxGinkgo partnership and to work with DTRA to make that future a reality."
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"Building on our achievements with STIMULON QS-21, SaponiQx is excited to realize our company's founding vision of harnessing the potential of Generative Molecular Design to dramatically increase access to lifesaving vaccines around the world," said Rebecca Kurnat, Head of Operations at SaponiQx.
The partners aim to demonstrate in the laboratory and in animal studies the ability of these novel adjuvants to protect against challenges from biothreat agents, such as the plague, and to provide lower cost, sustainable and scalable manufacturing processes by leveraging Ginkgo's leading platform for cell programming. The partners intend to design candidate adjuvants using SaponiQx's leading platform for adjuvant generation, and to identify additional candidates by screening natural extracts for previously uncharacterized saponins and creating non-natural saponins with enzyme-based techniques. Harnessing a first-of-its-kind "data lake" for adjuvants, they plan to use iterative GMD to propose and optimize adjuvant structures against eight functional parameters. Adjuvant candidates will be put through in-depth testing, first in the laboratory for immune and toxicity responses, and then in studies of their effectiveness in protecting vaccinated animals from pathogens; QS-21 and the related QS-7 will serve as benchmarks.
By leveraging Ginkgo's leading platform for cell programming, the partners also intend to develop more affordable, sustainable, and scalable adjuvant manufacturing processes. Ginkgo will develop a first-generation Adjuvant Development Candidate (ADC) production method, using a heterologous production strain such as brewers' yeast, Saccharomyces cerevisiae. Ginkgo's platform powers iterative DesignBuildTestLearn-driven cell engineering to enable the rapid prototyping, optimization, and development of proteins, enzymes, metabolic pathways, and whole organisms under commercial-scale manufacturing conditions. Development of a first-generation ADC production method could facilitate further development of a sustainable mass-production manufacturing process for these complex adjuvants.
About Ginkgo Bioworks
Ginkgo Bioworks is the leading horizontal platform for cell programming, providing flexible, end-to-end services that solve challenges for organizations across diverse markets, from food and agriculture to pharmaceuticals to industrial and specialty chemicals. Ginkgo's biosecurity and public health unit, Concentric by Ginkgo, is building global infrastructure for biosecurity to empower governments, communities, and public health leaders to prevent, detect and respond to a wide variety of biological threats. For more information, visitginkgobioworks.com andconcentricbyginkgo.com, read ourblog, or follow us on social media channels such as X (formerly known as Twitter) (@Ginkgo and @ConcentricByGBW), Instagram (@GinkgoBioworks and @ConcentricByGinkgo), Threads (@GinkgoBioworks) orLinkedIn.
About SaponiQx
Founded in 2021, SaponiQx, a subsidiary of Agenus Inc., stands at the forefront of saponin-based adjuvant discovery and manufacturing. Its mission is to provide scalable and affordable vaccine adjuvants to enhance global health. Its proprietary adjuvant, STIMULON QS-21, forms an integral part of the AS01 adjuvant used in several leading vaccines. STIMULON is a trademark of Agenus Inc., the parent company of SaponiQx Inc.
Forward-Looking Statements of Ginkgo Bioworks
This press release contains certain forward-looking statements within the meaning of the federal securities laws, including statements regarding the capabilities and potential success of Ginkgo's cell programming platform. These forward-looking statements generally are identified by the words "believe," "can," "project," "potential," "expect," "anticipate," "estimate," "intend," "strategy," "future," "opportunity," "plan," "may," "should," "will," "would," "will be," "will continue," "will likely result," and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including but not limited to: (i) volatility in the price of Ginkgo's securities due to a variety of factors, including changes in the competitive and highly regulated industries in which Ginkgo operates and plans to operate, variations in performance across competitors, and changes in laws and regulations affecting Ginkgo's business, (ii) the ability to implement business plans, forecasts, and other expectations, and to identify and realize additional business opportunities, (iii) the risk of downturns in demand for products using synthetic biology, (iv) the uncertainty regarding the demand for passive monitoring programs and biosecurity services, (v) changes to the biosecurity industry, including due to advancements in technology, emerging competition and evolution in industry demands, standards and regulations, (vi) our ability to realize the expected benefits of merger and acquisition transactions, (vii) the outcome of any legal proceedings against Ginkgo, including as a result of recent acquisitions, (viii) our ability to realize the expected benefits from and the success of our Foundry platform programs, (ix) our ability to successfully develop engineered cells, bioprocesses, data packages or other deliverables, and (x) the product development or commercialization success of our customers. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the "Risk Factors" section of Ginkgo's quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission (the "SEC") on November 8, 2023 and other documents filed by Ginkgo from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Ginkgo assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Ginkgo does not give any assurance that it will achieve its expectations.
GINKGO BIOWORKS INVESTOR CONTACT:
investors@ginkgobioworks.com
GINKGO BIOWORKS MEDIA CONTACT:
press@ginkgobioworks.com
Forward-Looking Statements of SaponiQx
This press release includes forward-looking statements, subject to risks and uncertainties, concerning the development of vaccines and adjuvants. Refer to the Risk Factors in Agenus' latest Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the SEC for a detailed discussion of these risks.
SAPONIQX MEDIA CONTACT:
communications@saponiqx.com
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SOURCE Ginkgo Bioworks
Preparation of mRNA
The antigen was designed using the DNA sequence encoding the spike protein of the SARS-CoV-2 Omicron variant. The mRNA vaccine plasmid was produced by inserting antigen DNA into multiple cloning sites on the mRNA platform using restriction enzymes (Pac1 and Cla1), as previously described46. After the mRNA vaccine template was linearized using Not1, mRNA was produced using the EZ T7 High Yield In vitro Transcription Kit (Enzynomics, Daejeon, Korea) according to the manufacturers protocol. Capping was performed using SC101 (STPharm, Siheung, Korea), and UTP was replaced with N1-methyl-pseudouridine (Trilink, San Diego, CA, USA). Total mRNA was precipitated using lithium chloride and purified using cellulose, as described previously47.
Lipid nanoparticles (LNPs) were prepared according to a reported protocol48. Briefly, all lipid components were dissolved in ethanol at a molar ratio of 50:10:38.5:1.5 (SM-102; distearoylphosphatidylcholine cholesterol, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000), and mRNAs were dissolved in sodium citrate buffer (50mM; pH 4) solution at a charge ratio of N/P=6. LNPs were formulated using NanoAssemblr IgniteTM (Precision Nanosystems, Vancouver, Canada) by mixing aqueous and organic solutions at a ratio of 3:1 and a total flow rate of 10mL/min. The LNP solution was concentrated by ultrafiltration using an Amicon Ultracentrifugal filter (UFC9030, Merck Millipore, Billerica, MA, USA), following the manufacturers instructions.
The size and Zeta potential of the mRNA vaccine were measured using a zetasizer with diluted mRNA vaccine in water (Zetasizer Nano Zs, Malvern Panalytical, Malvern, Worcestershire, UK). The encapsulation efficiency of LNP is determined by Ribogreen assay. Both Triton X-100 treated or untreated mRNA vaccines were incubated with Ribogreen reagent of Quant-it RiboGreen RNA Assay Kit (Thermofisher, Waltham, MA, USA, Cat. R11490). A microplate reader analyzed the fluorescence for the total and free mRNA amount. The following formula was used to obtain the encapsulation efficiency of the mRNA vaccine:
$${rm{Encapsulation; efficiency}}left( % right)=left[left({rm{Total}},{rm{mRNA}}-{rm{free}},{rm{mRNA}}right)/{rm{total}},{rm{mRNA}}right]times 100 %$$
The endotoxin level is determined to be lower than 0.1 EU/ml using the LAL assay kit (Cat. L00350, Genscript, Piscataway, NJ, USA).
Three microliter of mRNA vaccine solution was loaded onto a holey carbon grid (Quantifoil R1.2/1.3, 200 mesh Cu, Structure Probe Inc., USA) treated with a glow discharger at 15mA for 60s to increase the loading efficiency. The grid was blotted for 4s at 15C with 100% humidity using a Vitrobot Mark IV (Thermofisher, USA, SNU CMCI) and immediately plunge-frozen in liquid nitrogen-cooled liquid ethane. The grids were imaged with TEM (JEM-2100F, JEOL, Japan) while maintaining the temperature at ~180C at an acceleration voltage of 200keV. Images were recorded using an ultrascan 1000 electron detector.
Female Balb/c and C57BL6 mice at the age of 68 weeks were obtained from Dae-Han Biolink Co. (Eumseong, Korea) and housed in a controlled environment (inverted 12-h daylight cycle) with free access to food and water. All procedures were complied with the ARRIVE guidelines and approved by the Institutional Animal Care and Use Committee of the Samsung Biomedical Research Institute (#2022032201). The Samsung Biomedical Research Institute is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International and abides by the Institute of Laboratory Animal Resources guidelines. Mice were fed a normal-fat diet (containing 5% fat) and simultaneously treated with LPS from Escherichia coli (Sigma, St Louis, MO, USA). The surgical procedure for inserting the osmotic pump followed the manufacturers instructions. Briefly, after the hair was shaved, the back of the mouse was incised, and a space was made in the subcutaneous tissue. The device was inserted into the space, and the incision was closed using wound clips (7mm). The mice were implanted with an osmotic pump (Alzet model 1004; DURECT Corp., Cupertino, CA, USA) filled with either Tween-saline (0.9% NaCl and 0.1% Tween 80 in distilled water, Sigma), normal saline control, or LPS diluted in Tween-saline infused at 300g/kg/day for 4 weeks (LPS group)49. For blood collection, mice were anesthetized with isoflurane (Isotroy 100, Troikaa, Gujarat, India), and blood was collected from the facial vein. At the defined endpoint (2 days after the boost), mice were euthanized by CO2 inhalation, and their spleens, lungs, blood, hearts, and muscles were harvested.
The pump-implanted animals were randomly assigned to four groups for administering the intramuscular SARS-CoV-2 mRNA vaccine or normal saline control (groups: saline pump, saline pump + mRNA vaccine, LPS pump, and LPS pump + mRNA vaccine). The mice were immunized intramuscularly with 10g of the Omicron S mRNA vaccine with the sequence encoding the spike protein from the SARS-CoV-2 Omicron variant. The mRNA expression platform has been previously described22. The immunization schedule comprised two injections: an initial prime injection followed by a booster injection, with a 2-week interval between injections. Once the immunization protocol was completed, the mice were euthanized 2 days after immunization, and whole blood samples and tissues were collected.
Splenocytes (1106) isolated from immunized mice were cultured in 96-well plates. Subsequently, the samples were treated with Brefeldin A (Golgi plug, BD Biosciences, Franklin Lakes, NY, USA) and stimulated with antigen peptides of the spike protein from the SARS-CoV-2 Omicron variant (5g/mL) in RPMI medium for 12h at 37C. Then, the splenocytes were treated with anti-mouse CD16/32 (Invitrogen, Waltham, Massachusetts, USA) for 20min at 4C. To stain surface proteins such as CD8, the splenocytes were stained with anti-mouse CD8 fluorescent antibody for 30min at 4C in the dark. Then, the samples were fixed and permeabilized using BD Cytofix/Cytoperm (BD Biosciences), stained with anti-mouse tumor necrosis factor alpha (TNF-) and granzyme B fluorescent antibody for 30min at 4C in the dark. For detecting the levels of M1 and M2 macrophages in the lungs using flow cytometry, lung tissues excised from immunized mice were digested with Hanks Balanced Salt Solution containing 1.5mg/ml collagenase A, 0.1mg/ml Dnase1 (Sigma Aldrich, Burlington, Massachusetts, United States) for 1h at 37C and stained using anti-mouse CD11b, CD11c, and F4/80 with the surface protein staining method used for splenocytes. The samples were then fixed and permeabilized using a Foxp3 Fixation Kit (Invitrogen) according to the manufacturers instructions. The cells were stained with anti-mouse CD206 CD8 fluorescent antibody in the dark for 30min at 4C. The samples were analyzed using a CytoFlex flow cytometer (Beckman Coulter, Brea, CA, USA), and data were analyzed using CytExpert (Beckman Coulter, Brea, CA, USA).
Enzyme-linked immunosorbent assays (ELISAs) were performed to assess antigen-specific total IgG levels in mouse serum. Briefly, a 96-well plate was coated with S protein from the SARS-CoV-2 Omicron variant at a concentration of 100ng/well and incubated overnight at 4C. The wells were then blocked with 100l blocking buffer (1% BSA in PBS) for 1h at room temperature. The serum samples diluted with blocking buffer (at 1:20) were added to the wells and incubated for 2h at room temperature (2022C). After the incubation period, the wells were washed thrice with 200l PBS-T (PBS containing Tween 20). Horseradish peroxidase-conjugated anti-mouse IgG antibodies (from Bethyl Laboratories, Montgomery, TX, USA) were added to the wells and then the plates were incubated at room temperature for 1h. The antibodies were appropriately diluted in blocking buffer (at 1:5000). Following three washes with PBS-T, tetramethylbenzidine substrate was added to the wells, and the plates were incubated for 15min. The reaction was stopped by adding 2N H2SO4. Finally, the optical density was measured at 450nm using a microplate reader (GloMax Explorer, Promega, Seoul, Republic of Korea).
Splenocytes (5105) isolated from immunized mice were cultured in 96-well MultiScreen-IP Filter Plates (Millipore, Burlington, MA, USA) and stimulated with antigen peptides of spike protein from the Wuhan SARS-CoV-2 strain (5g/ml) in RPMI medium for 24h at 37C. The ELISpot assay for detecting IFN- secreted from splenocytes was performed as per the manufacturers instructions (Mab-tech, Stockholm, Sweden).
The epididymal fat, liver, lung, muscle, and pancreatic tissues of osmotic pump-implanted mice were fixed in 10% neutral formalin. After fixation, the samples were embedded in paraffin and stained with hematoxylin and eosin (H&E). The percentage area of myocardial inflammation was determined using computer-assisted analysis. Two different areas of each heart were quantified using ImageJ software1.45s (NIH, MA, USA), as described previously50. To analyze the damaged muscle area, a Motic EasyScan Digital Slide Scanner (Motic Hong Kong Ltd., Hong Kong, China) was used to randomly capture 510 images of the affected regions. These images were then analyzed for the cross-sectional area (CSA) of the centrally nucleated regenerating myofibers using ImageJ software51. The procedures were performed by investigators who were blinded to the identities of the samples. In the SARS-CoV-2 spike immunohistochemistry procedure, Dako Retrieval Solution (pH 6.0, S2369) was utilized for antigen retrieval through incubation of sections. To mitigate nonspecific binding, a blocking step of 1-hour duration was carried out using Dako Protein Block Serum-Free (X0909). Subsequently, the sections were exposed to anti-SARS-CoV/SARS-CoV-2 (COVID-19) spike antibody (1:200; GTX632604, GeneTex) for 24h at 4C. The visualization of antigens was enabled using the Dako Envision Detection system Peroxidase/DAB+ (K5007). Following this, the slides were dehydrated and mounted after counterstaining with hematoxylin. Images of the SARS-CoV-2 spike protein were captured randomly using a Motic Easyscan Digital Slide Scanner (Motic Hong Kong Limited).
Total RNA was extracted from lung tissue using the TRIzol reagent (Invitrogen, Grand Island, NY, USA), and cDNA was synthesized using a cDNA synthesis kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturers instructions. Real-time PCR was performed using the SYBR Green Master Mix (Applied Biosystems, Foster City, CA, USA) to compare the mRNA levels of genes associated with inflammation, myogenesis, muscle types, and mitochondria. The primer sets were synthesized by SFC-probe (Cheongju, Korea) for inflammation-related genes and Bioneer (Daejeon, Korea) for the remaining genes. The primer sequences are listed in Supplementary Table 1.
Plasma was isolated from mouse blood and processed according to the manufacturers protocol for the Creatine Kinase Activity Assay Kit (3050 Spruce Street, St. Louis, MO, USA). The creatine kinase activity was determined by measuring absorbance (340nm) using a VICTOR Nivo TM multimode Microplate Reader (PerkinElmer, Waltham, MA, USA) following the standard procedure for assessment.
Statistical analyses were performed using Prism 8 software (GraphPad, San Diego, CA, USA). Data were presented as meanstandard deviation. Significant differences between means were determined using Students t-test, and P values less than 0.05 were considered statistically significant.
Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Limited data exist on the safety and efficacy of vaccines for pregnant women living with HIV (PWLWH), which can lead to difficult policy decisions for this population, according to a review published in eClinicalMedicine. PWLWH should be the focus of studies in the future, the authors conclude.
Mother-to-child transmission of HIV has been largely eliminated due to the usage of combined antiretroviral therapy (cART). The estimated 5.4 million children worldwide who are HIV-exposed but uninfected (HEU) often have vulnerability to other infections. Vaccine trials often do not include pregnant women, especially PWLWH who could benefit from the vaccines to protect their infants. This study aimed to assess the safety and efficacy of vaccines that were given to PWLWH that could reduce the morbidity and mortality of HEU.
Pregnant woman | Image credit: pressmaster - stock.adobe.com
MEDLINE, Embase, Web of Science, Virtual Health Library, and Cochrane Library were used to search for studies that involved the safety and efficacy of vaccines given to PWLWH. The search specifically looked for randomized controlled trials and observational studies that took place between the inception of the database and September 6, 2023. Studies were eligible if the study included a vaccine being given to a PWLWH during their pregnancy with a controlled group of women who were not living with HIV. Studies were excluded if they were review articles, a case series, conference abstracts, letters, or animal studies.
Data extracted from the studies included the HIV status of the mother, treatment they received, gestational age at the time of vaccine distribution, and the formulation of the vaccination that was given.
There were 12 studies included in the final analysis which included 3744 pregnant women, of which 1714 were PWLWH. The studies came from South Africa, Brazil, and Malawi. Pneumococcal, influenza, and group B streptococcus vaccines were tested in this population.
There were 5 studies that reported on the safety of the vaccines in 3456 pregnant women, of which 1250 were PWLWH. A total of 4.1% of PWLWH reported at least 1 severe local reaction and 18.6% reported at least 1 severe systemic reaction in 1 of the studies. This is compared with pregnant women without HIV, who reported at least 1 severe local reaction in 5% of cases and at least 1 severe systematic reaction in 15% of cases. An increased rate of injection site reactions were reported in a separate study. The most common severe adverse event was preterm births, which occurred in 17% of PWLWH compared with 10% of pregnant women without HIV.
Antibodies in PWLWH from vaccines were found to be lower compared with pregnant women without HIV after 4 weeks, even though the antibodies increased in PWLWH from baseline. The pooled mean difference in the concentration of antibodies from before the vaccination to 28 to 35 days after found that there was an increase in the concentration of antibodies in the 3 studies that did the analysis. However, when comparing PWLWH to pregnant women without HIV, the latter were found to have significantly higher antibody concentration compared with PWLWH (mean difference, 141.8; 95% CI, 194.9 to 88.6).
There were some limitations to this study. The PWLWH who were included in this study make up a small percentage of the overall population of PWLWH. The methodological quality of the studies was important to the findings. The results of only 3 studies were able to be pooled for the meta-analysis. None of the studies used in the review used the Global Alignment of immunization criteria to measure the safety of vaccines.
The researchers concluded that more data on vaccine safety in pregnant women is necessary for any new vaccines coming to the market. The availability of uniform accurate data and standardized definitions will improve maternal vaccine confidence especially in special sub-populations such as PWLWH who may require different vaccine formulations or schedules to keep themselves and their infants protected, the authors wrote.
Reference
Nakabembe E, Cooper J, Amaral K, et al. The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis. eClinicalMedicine. 2024;69:102448. doi:10.1016/j.eclinm.2024.102448
