Virus World

The pharma, once a frontrunner in the race to develop the first vaccine for the respiratory virus, said it will end a 23,000-person study of its experimental shot amid a restructuring of its infectious disease division.

Dive Brief:

• Johnson & Johnson will stop developing its experimental vaccine for respiratory syncytial virus in an unexpected retreat from a high-profile research effort that had put the pharmaceutical giant among the leading companies seeking to win the first approval of a preventive shot.
• The company said Wednesday it will discontinue a 23,000-person Phase 3 trial, called Evergreen, of its RSV vaccine in adults following a review of its drug pipeline. The company does not plan to develop the shot for pregnant women or infants, a spokesperson confirmed.
• J&J’s pullback comes amid a restructuring of its infectious disease division, which was reported by Fierce Pharma in February. Its decision also thins the RSV vaccine competition, leaving GSK and Pfizer in the lead with shots that are currently under review by the Food and Drug Administration. Moderna is also developing an RSV vaccine and could file for approval this year.

BACKGROUND

The Ad26.COV2.S vaccine was highly effective against severe–critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis.

METHODS

We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed.

RESULTS

Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe–critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe–critical Covid-19 (with only 4 severe–critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19–related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified.

CONCLUSIONS

A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe–critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722. opens in new tab.)

Published in NEJM (Feb. 9, 2022):

https://doi.org/10.1056/NEJMoa2117608 

A two-dose version of Johnson & Johnson's coronavirus vaccine provides 94% protection against symptomatic infection, the company said Tuesday -- making a two-dose regimen of J&J's Janssen vaccine comparable to a two-dose regimen of Moderna's or Pfizer's.  Plus, the company said, adding a booster dose to a single shot of the vaccine raised immunity even more, and should also protect people strongly against infection. The company released some details of three studies looking at various aspects of its Janssen vaccine, and said that, taken together, they showed the vaccine provided long-lasting protection that could be boosted with an extra shot. "Our large real-world-evidence and Phase 3 studies confirm that the single-shot Johnson & Johnson vaccine provides strong and long-lasting protection against COVID-19-related hospitalizations," Dr. Mathai Mammen, global head of Janssen Research & Development, said in a statement.  "Our single-shot vaccine generates strong immune responses and long-lasting immune memory. And, when a booster of the Johnson & Johnson COVID-19 vaccine is given, the strength of protection against COVID-19 further increases." Johnson & Johnson's single-dose vaccine was given emergency use authorization by the US Food and Drug Administration on February 27. It has been given to about 14.8 million Americans, according to the US Centers for Disease Control and Prevention.

Some people who received the Johnson & Johnson Covid-19 shot in the U.S. are seeking out added doses of a messenger-RNA vaccine, fearing their initial inoculation won’t protect them from the virus. Demand for the one-and-done J&J shot has suffered in part due to the perception that it’s inferior to the two-dose mRNA vaccines that showed higher efficacy in clinical trials. But it is unclear if mixing vaccines will safely increase protection, and there are fresh signs that J&J’s shot is a strong shield against variants. Last month, the first suggestion that mixing may be helpful came in a study that found combining the Pfizer Inc.-BioNTech SE vaccine with AstraZeneca Plc’s shot, which is based on adenovirus vector technology similar to J&J’s vaccine, can provide a formidable shield against infection. The U.S. Centers for Disease Control and Prevention recommends people don’t mix vaccines until robust clinical data validates the benefit and quells concerns about risks. Anthony Fauci, the top federal infectious-disease expert, said at a Thursday White House briefing that there’s “no real fundamental scientific reason to do that right now.” But anxiety about the highly transmissible delta variant that’s sweeping across the U.S., along with emerging data on the mix-and-match approach, has led some people, including pharmaceutical executives and the immunocompromised, to act.

Terri Leslie is a case in point. She considers herself risk-averse when it comes to Covid. She has spent most of the pandemic in quarantine, ordering groceries online and avoiding gatherings. To get the message across, she recently bought a T-shirt, stating in capital letters, “When this virus is over, I still want some of you to stay away from me.” But Leslie was willing to try the mix-and-match strategy. The Mills River, North Carolina, resident jumped at the opportunity to get the J&J shot in March when a hospital called her and offered it. Since then, she’s lamented not receiving a mRNA vaccine. Leslie, 61, takes a rheumatoid arthritis medication that’s left her immune-suppressed, and she was worried about contracting the virus.  “I don’t want to live in fear of getting sick,” Leslie said. On Tuesday, Leslie decided to take matters into her own hands. Like others before her, she’d been scrolling through tweets from biochemists, virologists and infectious-disease experts advocating that J&J recipients boost their immunity with an mRNA vaccine. Sure, there was backlash on Twitter. But with the blessing of her pediatrician husband, Leslie went to her primary care doctor and received a prescription for the Pfizer vaccine. The pharmacist hesitated when presented with the prescription, she said, and stepped aside to research the issue. His comment when he returned, according to Leslie: “We’re flying in the dark.” But he then administered the first dose, and she is set to get her second in three weeks. “Whatever we can do to protect ourselves, we must do it before it’s too late,” Leslie said. “Nobody is wearing masks anymore.”  U.S. health agencies are monitoring the phenomenon. CDC Director Rochelle Walensky said on a podcast with Andy Slavitt, a former adviser to the Biden administration on the virus response, that she’s aware of the concerns about the J&J vaccine. “Some people have said, ‘I’m just not going to tell anyone and I’m going to get an mRNA vaccine,’” she said. “We don’t have a huge amount of data on the safety or the side effect profile of getting the mRNA vaccine after Johnson & Johnson, or really the effectiveness of that approach.” Still, when pressed by Slavitt, Walensky said, “It’s probably safe. But they are generating data to inform us one way or another.” That data could come from a National Institutes of Health trial launched in June in which fully vaccinated adults will receive booster doses of different Covid-19 vaccines. Similar studies are being conducted outside the U.S. as well, with the idea that mixing vaccines may not only be able to strengthen immunity in some people, but could could help overcome shortages in areas where it may be difficult to reliably obtain vaccine supplies. “The situation right now is that people locally will be making those kinds of decisions, but you should only be making a formal recommendation based on clinical data,” said Fauci, the director of the National Institute of Allergy and Infectious Diseases, at the White House briefing. “When those data become available, you will see recommendations change according to the data.”

Delta Performance

J&J’s vaccine hasn’t yet produced efficacy data against the delta variant that was first identified in India. But on Thursday J&J said its vaccine showed strong neutralizing antibodies for at least eight months against all variants including delta in a small number of clinical-trial participants. Company officials dismissed the idea that their shot needed to be supplemented with another vaccine. “There’s no reason or indication to do that to get full protection for severe disease, hospitalization or death,” said Paul Stoffels, J&J’s chief scientific officer, in an interview. “That has been clearly studied, and I wouldn’t recommend any other approach until the data have been generated. At the moment it’s all speculation.” The company reported that the vaccine prompted a more robust immune response against the delta variant than even against the beta variant that was first detected in South Africa. Only a single shot of the J&J vaccine is currently needed to shield against variants, Stoffels said, noting that J&J will evaluate boosting protection with its own formulation down the line. Still, assurances from U.S. health officials and J&J that the vaccine continues to work haven’t stopped doctors and patients from theorizing about the potential benefits of mixing shots. Interchanging vaccines of the same type -- such as those made using mRNA technology -- isn’t likely to provide an advantage over a standard two-dose course of one of them. But mixing vaccines that use different platforms, through a process known as heterologous prime-boosting, could offer a benefit, according to some scientists. Different vaccine platforms could activate the immune system in different ways, they suggest, and mixing them up might generate immune responses that stimulate each other at a granular level.

Three Concessions

Paul Sax, clinical director of the division of infectious diseases at Brigham and Women’s Hospital in Boston, continues to be approached by his peers and patients on what J&J recipients should do to bolster protection. When advising them, he makes three concessions: First, J&J’s shot is less effective than the mRNA doses. Second, data from the U.K. show those most protected from the delta variant got two doses. And third, a study suggested you can boost an adenovirus-based vaccine like J&J’s with an mRNA version and see a good response. After being presented with that information, one of Sax’s patients chose to move forward with a J&J-plus-mRNA regimen. Another decided to wait to see what happens over the summer since so few virus cases are currently being reported in New England. “There’s a very good argument to be made that it’s worth doing, but since we don’t have any definitive data yet I can understand why it’s not formally in the guidelines,” Sax said.

Unvaccinated America

The Biden administration, meanwhile, is focused on increasing the number of people getting shots in unvaccinated pockets of the country. The gap between the most vaccinated and least vaccinated places in the U.S. has widened despite efforts to convince more Americans to get a Covid-19 shot. Health-care providers in areas where interest is low see a significant role for the J&J vaccine. It can be stored in a refrigerator for long periods, making it a useful tool for pop-up clinics and mobile vaccine units. And because it’s a single shot, it’s an appealing option to those who can’t take multiple days off work. “The public health goal is to prevent hospitalization, severe disease, and death, and so far, Johnson & Johnson has held up as 100% effective against those things,” said Shereef Elnahal, the chief executive officer of University Hospital in Newark, New Jersey. “Our main focus now should be to get J&J to more people in the community. We shouldn’t lose focus on that.”

— With assistance by Angelica LaVito, Shira Stein, and Jeannie Baumann

The doses, produced at a Baltimore factory under federal review, could have been contaminated.  Federal regulators have told Johnson & Johnson that about 60 million doses of its coronavirus vaccine produced at a troubled Baltimore factory cannot be used because of possible contamination, according to people familiar with the situation. The Food and Drug Administration plans to allow about 10 million doses to be distributed in the United States or sent to other countries, but with a warning that regulators cannot guarantee that Emergent BioSolutions, the company that operates the plant, followed good manufacturing practices. The agency has not yet decided whether Emergent can reopen the factory, which has been closed for two months because of regulatory concerns, the people said. The Johnson & Johnson doses administered in the United States so far were manufactured at the firm’s plant in the Netherlands, not by Emergent. For weeks the F.D.A. has been trying to figure out what to do about at least 170 million doses of vaccine that were left in limbo after the discovery of a major production mishap involving two vaccines manufactured at the Baltimore factory.

• COVID-19 vaccines from Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca all have unique features.
• They varyin effectiveness, side effects, dosage, and ages approved for the shots.
• Here is a table that compares them all. Scroll down to view it.

Coronavirus vaccines are the world's escape route out of a pandemic that has shut down schools, grounded flights, and left millions dead. Vaccines from Moderna, Pfizer-BioNTech, AstraZeneca-Oxford University, and Johnson & Johnson have been approved in the West. In the US, all of them have been authorized except AstraZeneca's — in the UK, all of them except Johnson & Johnson's are authorized. Each is given as a shot in the muscle of the upper arm. You might not get a choice about which COVID-19 vaccine you get, but all four offer some protection against severe illness, so the advice is to take one if you are offered it. For the two-dose vaccines, you should have two shots of the same one, where possible.  Speak with your doctor if you are pregnant, breastfeeding, have a specific medical condition, or take medicines —especially if they thin your blood or affect your immune system. Experts have said the COVID-19 vaccines won't make you infertile. Side effects may start within a day or two and should go away within a few days.  We've made a table that gives you the key information for each shot, whether you've booked an appointment or not. Scroll down to view it.

F.D.A. studies show the shot strongly protects against severe illness and may reduce spread of the virus. But the drugmaker has fallen short of initial production goals.  The coronavirus vaccine made by Johnson & Johnson provides strong protection against severe disease and death from Covid-19, and may reduce the spread of the virus by vaccinated people, according to new analyses released Wednesday by the company and the Food and Drug Administration. The reports provided confirmation of the initial results announced by Johnson & Johnson late last month, indicating that the United States is likely to soon have access to a third coronavirus vaccine developed in under a year. The F.D.A. could authorize the vaccine as early as Saturday, depending on a vote by its vaccine advisory panel on Friday, and distribution could begin within days. If cleared, the vaccine would reach a number of firsts for the U.S. pandemic. Unlike the authorized vaccines made by Pfizer-BioNTech and Moderna, which require two doses, Johnson & Johnson’s is just a single shot, allowing the number of fully vaccinated Americans to rapidly increase once it is deployed. More than 44 million Americans have received at least one dose of the Moderna and Pfizer vaccines, but only around 20 million have received a second dose. Those earlier vaccines use a new technology called mRNA that needs freezers for long-term storage. Johnson & Johnson’s vaccine, which uses sturdier viruses to deliver genes into cells, can keep for three months at normal refrigeration temperatures, making it easier to distribute and easier for pharmacies and clinics to stock. The White House on Wednesday said around two million doses would be ready to allocate to states next week, with up to another two million for pharmacies and community health centers.

The documents published by the F.D.A. on Wednesday showed that the new vaccine had an overall efficacy rate of 72 percent in the United States and 64 percent in South Africa, where a concerning variant emerged in the fall that is now driving most cases. The efficacy in South Africa was seven percentage points higher than earlier data released by the company showed. The vaccine also showed 86 percent efficacy against severe forms of Covid-19 in the United States, and 82 percent against severe disease in South Africa. That means that a vaccinated person has a far lower risk of being hospitalized or dying from Covid-19. None of the nearly 22,000 vaccinated people in the trial died of Covid-19. “The vaccine has definitely met the bar of what’s worthy of rolling out and using. It’s performing well,” said Natalie Dean, a biostatistician at the University of Florida. Another authorized vaccine, and especially one that only requires one dose, could block the spread of the virus more effectively and drive down cases faster. “Having more products available is a huge advantage,” Dr. Dean said. State health departments around the nation have been eager to take advantage of it. In North Dakota, which has one of the nation’s highest rates of vaccination, members of the state’s vaccine ethics committee met this week to discuss the allocation and distribution of the vaccine, anticipating the F.D.A.’s analysis, said Kylie Hall, a vaccine adviser for the state’s health department. The new data may help guide the state’s decisions on which people to prioritize for the small number of doses that may arrive next week, she said.  “It prevents severe disease and death from Covid,” she said. “That’s the best news we could have.” But access to the new vaccine could be limited at first. Dr. Richard Nettles, the vice president of U.S. medical affairs at Janssen Pharmaceuticals, the drug development arm of Johnson & Johnson, told lawmakers on Tuesday that nearly four million doses would be ready for shipment if the F.D.A. authorizes the vaccine. That is far below the 12 million it had originally pledged to give the federal government by the end of February. He said that a total of 20 million doses would be ready by the end of March, 17 million fewer doses than the firm’s federal contract envisioned. But he insisted that Johnson & Johnson would fulfill its promise of 100 million doses by the end of June.

Johnson & Johnson’s vaccine has a lower efficacy rate than the vaccines from Moderna and Pfizer-BioNTech, which are both around 95 percent. But in South Africa, the Johnson & Johnson vaccine is so far the clear winner. Novavax’s shot had an efficacy of 49 percent in South Africa. And a small trial in South Africa of the AstraZeneca-Oxford vaccine found that it did not offer much protection at all. The negative results led the South African government to abandon its plan of giving a million doses of AstraZeneca vaccines to health care workers. Last week, the government started giving Johnson & Johnson’s vaccines instead, and has so far administered more than 32,000. The newly released documents, which include the F.D.A.’s first technical analysis of the company’s 45,000-person clinical trial, presented evidence that the vaccine was safe, with noticeably milder side effects than the Pfizer and Moderna vaccines and without any reports of severe allergic reactions like anaphylaxis.  The vaccine’s protection was consistent across Black, Hispanic and white volunteers, and also across different ages. The trial estimated a lower efficacy, of 42.3 percent, for people over 60 who had risk factors like heart disease or diabetes, a figure that came with a large amount of statistical uncertainty, the F.D.A. noted....

AstraZeneca Plc's COVID-19 vaccine trial in the United States is expected to resume as early as this week after the U.S. Food and Drug Administration completed its review of a serious illness in a study participant, four sources told Reuters. AstraZeneca’s large, late-stage U.S. trial has been on hold since Sept. 6, after a participant in the company’s UK trial fell ill with what was suspected to be a rare spinal inflammatory disorder called transverse myelitis. The sources, who were briefed on the matter but asked to remain anonymous, said they have been told the trial could resume later this week. It was unclear how the FDA would characterize the illness, they said. An FDA spokeswoman declined to comment.

The agency is requiring researchers conducting the trial to add information about the incident to consent forms signed by study participants, according to one of the sources.  The agency is requiring researchers conducting the trial to add information about the incident to consent forms signed by study participants, according to one of the sources. “In this case, after considering the information, the independent reviewers and MHRA (Medicines and Healthcare products Regulatory Agency) recommended that vaccinations should continue,” the draft consent form stated. “Close monitoring of the affected individual and other participants will be continued.” Regulators in Brazil, India and South Africa also previously allowed AstraZeneca to resume its vaccine trials there.

AstraZeneca, which is developing the vaccine with Oxford University researchers, had been seen as a frontrunner in the race to produce a vaccine for COVID-19 until its trials were put on hold to investigate the illness. Early data from large-scale trials in the United States of vaccines from Pfizer Inc PFE.N and Moderna Inc MRNA.O are expected some time next month. Johnson & Johnson JNJ.N last week paused its Phase III COVID-19 vaccine trial to investigate an unexplained illness in a study participant. At the time of the announcement, the company did not know whether the volunteer had been given its vaccine or a placebo. A J&J spokesman on Tuesday said the study remains on pause as the company continues its review of medical information before deciding to restart the trial. J&J noted last week that its “study pause” was voluntary. By contrast, AstraZeneca’s trial is on “regulatory hold,” which is imposed by health authorities...

The study of Johnson & Johnson’s Covid-19 vaccine has been paused due to an unexplained illness in a study participant. A document sent to outside researchers running the 60,000-patient clinical trial states that a “pausing rule” has been met, that the online system used to enroll patients in the study has been closed, and that the data and safety monitoring board — an independent committee that watches over the safety of patients in the clinical trial — would be convened. The document was obtained by STAT. Contacted by STAT, J&J confirmed the study pause, saying it was due to “an unexplained illness in a study participant.” The company declined to provide further details. “We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information,” the company said in a statement.

J&J emphasized that so-called adverse events — illnesses, accidents, and other bad medical outcomes — are an expected part of a clinical study, and also emphasized the difference between a study pause and a clinical hold, which is a formal regulatory action that can last much longer. The vaccine study is not currently under a clinical hold. J&J said that while it normally communicates clinical holds to the public, it does not usually inform the public of study pauses. The data and safety monitoring board, or DSMB, convened late Monday to review the case. J&J said that in cases like this “it is not always immediately apparent” whether the participant who experienced an adverse event received a study treatment or a placebo. Though clinical trial pauses are not uncommon — and in some cases last only a few days — they are generating outsized attention in the race to test vaccines against SARS-CoV-2, the virus that causes Covid-19.

Given the size of Johnson & Johnson’s trial, it’s not surprising that study pauses could occur, and another could happen if this one resolves, a source familiar with the study said.

“If we do a study of 60,000 people, that is a small village,” the source said. “In a small village there are a lot of medical events that happen.” On Sept. 8, a large study of another Covid-19 vaccine being developed by AstraZeneca and Oxford University was put on hold because of a suspected adverse reaction in a patient in the United Kingdom. It’s believed that the patient had transverse myelitis, a spinal cord problem. Studies of the vaccine resumed roughly a week after it was paused in the United Kingdom, and have since been restarted in other countries as well. It remains on hold, however, in the United States. Johnson & Johnson began enrolling volunteers in its Phase 3 study on Sept. 23. Researchers planned to enroll 60,000 participants in the United States and other countries.

Although none of the coronavirus vaccines under development has proved its efficacy yet in clinical trials, at least 5.7 billion doses have been pre-ordered  around the world. First shipments of a COVID-19 vaccine created by Western laboratories have often been snapped up by the United States. Five vaccines — three Western and two Chinese — are in Phase 3 efficacy trials involving thousands of people. In a surprise announcement, Russian President Vladimir Putin claimed Tuesday that a vaccine dubbed Sputnik V — after the Soviet satellite — conferred “sustainable immunity” against the novel coronavirus. As research laboratories around the world race to develop a vaccine, manufacturers have received financing to help them prepare to have millions of doses ready to administer in 2021 or even before the end of the year.

Oxford University, working with the Swedish-British pharmaceutical group AstraZeneca, hopes to have results by September, while the US biotech company Moderna, partnering with the U.S. National Institutes of Health (NIH), is aiming for the end of the year, possibly November. U.S. President Donald Trump has launched “Operation Warp Speed” in a bid to develop, manufacture and distribute a COVID-19 vaccine to all Americans by January 2021. Hundreds of millions of dollars have been directed to vaccine developers, including nearly $500 million to Johnson & Johnson at the end of March. The United States has allocated funding to more companies than any other nation in the hope that one of them will come up with the vaccine to counter the highly contagious virus. So far, Washington has handed out at a total of at least $9.4 billion to seven vaccine developers and signed manufacturing contracts with five of them to provide 700 million doses. The companies involved are: Johnson & Johnson, Moderna, Oxford/AztraZeneca, Novavax, Pfizer/BioNTech, Sanofi/GSK, Merck Sharp and Dohme.  Two vaccine developers — Oxford/AztraZeneca and Sanofi/GSK — have signed or are in advanced negotiations with the European Commission to provide a combined 700 million vaccine doses. Britain, because of Brexit, is negotiating a separate pre-order of 250 million doses from four developers.  Japan is counting on 490 million doses from three suppliers, including 250 million from Novavax of the United States. Pharmaceutical giant Takeda bought the rights to a Novavax vaccine for Japan, which has funded the research. It would be produced locally.

Brazil chose a similar model, ordering 100 million doses from AstraZeneca and partnering with China’s Sinovac to produce 120 millions of CoronaVac, which is already undergoing testing with Brazilians. Clinical tests of two Chinese vaccine candidates — Sinovac and Sinopharm — are well underway but only a few international partnerships have been announced, the one with Brazil and a possible one with Indonesia. Russia said 20 nations have pre-ordered 1 billion doses of Sputnik V and that with foreign partners it would be able to produce 500 million doses a year in five countries. The Coalition for Epidemic Preparedness Innovations, launched in 2017 by Norway, India, the Bill and Melinda Gates Foundation and the Wellcome Trust, seeks to ensure that there is “equitable access” to future vaccines. It has pre-ordered 300 million doses from AstraZeneca for dozens of developing countries in a partnership with The Vaccine Alliance. Billions of doses would be produced for Asia and elsewhere by the giant Serum Institute of India (SII), the largest vaccine producer in the world. Novavax and AstraZeneca have separately signed agreements with SII to produce a billion doses each for India and low- and middle-income countries on the condition that they prove their efficacy in clinical trials.

Question  Are Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccines associated with Guillain-Barré syndrome (GBS) within 21 or 42 days after vaccination?

Findings  This cohort study of 487 651 785 COVID-19 vaccine doses found that in observed-to-expected analyses, the observed number of GBS reports was higher than expected based on background rates within 21 and 42 days after vaccination for Ad26.COV2.S but not BNT162b2 or mRNA-1273. GBS reporting rates within 21 and 42 days of Ad26.COV2.S vaccination were 9 to 12 times higher than after BNT162b2 or mRNA-1273 vaccination.

Meaning  These findings suggest that Ad26.COV2.S vaccination was associated with GBS and that GBS after BNT162b2 and mRNA-1273 may represent background incidence.

Importance  Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring.

Objective  To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines.

Design, Setting, and Participants  This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included.

Exposures  Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine.

Main Outcomes and Measures  Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates.

Results  Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods.

Conclusions and Relevance  This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

Vaccine advisers to the US Food and Drug Administration voted unanimously Friday to recommend a booster dose of Johnson & Johnson's vaccine at least two months after people get the first dose. The FDA's Vaccines and Related Biological Products Advisory Committee voted 19-0 to recommend the extra dose for all recipients of the J&J Janssen vaccine, 18 and older. They asked to simplify the original question being posed by the FDA, which had asked the committee to say whether the data showed that waiting six months or longer after getting the first shot would provide an even stronger immune response. The FDA will now consider the committee's advice. Then the US Centers for Disease Control and Prevention's vaccine advisers will be asked to consider it.  Johnson & Johnson says studies have shown boosting at two or six months can bring that effectiveness up to 94% and it says its effectiveness does not wane over time in the same way that effectiveness from Pfizer's vaccine does. But the Johnson & Johnson vaccine has not been shown to be as protective as either the Pfizer or Moderna vaccines, noted VRBPAC chair Dr. Arnold Monto, a professor of public health and epidemiology at the University of Michigan. "So there is some urgency here to do something," he told the meeting. And the CDC's Dr. Amanda Cohn told the meeting that various studies suggested real-world efficacy of J&J's vaccine was anywhere between 50% and 68%.

"Regardless of whether or not there been waning or this is the true effectiveness after a single dose, the effectiveness or protection of a single dose of the J&J vaccine is not equivalent to protection at this time with either two doses of an mRNA vaccine and certainly not in those groups who have now been authorized to receive a booster dose of an mRNA vaccine," Cohn said.  Members of the committee said while there was not much data to show whether the efficacy of the Janssen vaccine was waning -- or was strong to begin with -- they agreed people should be given the opportunity for a booster. "I would say I agree a second dose booster is needed to boost immunity back to the 90-plus range," Dr. Archana Chatterjee, a pediatric infectious diseases expert at Rosalind Franklin University in Chicago, said before the vote. The FDA has already given EUA to a booster for Pfizer's vaccine for people who are six months out from their first two shots who are also either 65 or older or who are at least 18 and have a higher risk of severe disease because of pre-existing conditions or because of work or living conditions. And Americans are already flocking to get those boosters. Data from the US Centers for Disease Control and Prevention show close to 5% of fully vaccinated people -- about 9 million people -- have received booster shots.

On Thursday, VRBPAC members voted unanimously to recommend booster doses of Moderna's vaccine to the same groups. If the FDA gives emergency use authorization to Moderna or Johnson & Johnson boosters, CDC vaccine advisers will meet to discuss which groups to recommend them to. Typically, shots can be administered once the CDC director signs off on the recommendation. CDC's Advisory Committee on Immunization Practices is scheduled to discuss boosters on October 21.

With concerns surrounding the Delta coronavirus variant rising globally, how effective are the current vaccines in the U.S. at protecting against the new version of the virus? According to medical experts, the three vaccines currently available each offer protection. Here’s a breakdown of each vaccine and what you should know: How effective are the COVID vaccines overall? In clinical trials, Moderna’s  In clinical trials, Moderna's vaccine reported 94.1% effectiveness at preventing COVID-19 in people who received both doses. The Pfizer-BioNTech vaccine was said to be 95% effective. A new CDC study reported that a single dose of Pfizer's or Moderna's COVID vaccine was 80% effective in preventing infections. That number jumped to 90% two weeks after the second dose, the study on vaccinated health care workers showed.  "These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions," the U.S. agency wrote in the study. "COVID-19 vaccination is recommended for all eligible persons." Pfizer's vaccine, the only one currently authorized for use in children as young as 12, also showed heightened effectiveness among adolescents.  Pfizer in late March released preliminary results from a vaccine study of 2,260 U.S. volunteers ages 12 to 15, showing there were no cases of COVID-19 among fully vaccinated adolescents compared with 18 among those given dummy shots. More intriguing, researchers found the kids developed higher levels of virus-fighting antibodies than earlier studies measured in young adults. The FDA said J&J’s vaccine offers strong protection against what matters most: serious illness, hospitalizations and death. One dose was 85% protective against the most severe COVID-19 illness, in a massive study that spanned three continents — protection that remained strong even in countries such as South Africa, where the variants of most concern were spreading at the time.  The CDC reports J&J/Janssen vaccine was 66.3% effective in clinical trials at preventing COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. "The vaccine had high efficacy at preventing hospitalization and death in people who did get sick," the CDC notes. "No one who got COVID-19 at least four weeks after receiving the J&J/Janssen vaccine had to be hospitalized." It is not known if any of the three vaccines prevent the spread of the virus by people who are asymptomatic, though the CDC noted that "early evidence suggests that the J&J/Janssen vaccine might provide protection against asymptomatic infection." 

How effective are the vaccines against the new Delta variant?

Data surrounding vaccine effectiveness with the Delta variant is so far limited. While studies have shown that the available vaccines work against variants, including the Delta variant, all two-dose vaccines offer significantly more protection following their second dose. Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the Alpha variant that was first detected in the U.K. The vaccines were protective for those who got both doses but were less so among those who got one dose. One recent study showed the Pfizer vaccine was 84% effective against the variant after two doses, but only 34% effective after the first dose.  Moderna also announced Tuesday that a new study showed its vaccine also produced promising protection in a lab setting against the Delta variant and others currently circulating. “As we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. We remain committed to studying emerging variants, generating data and sharing it as it becomes available. These new data are encouraging and reinforce our belief that the Moderna COVID-19 Vaccine should remain protective against newly detected variants,” Stéphane Bancel, chief executive officer of Moderna, said in a statement. Currently, little data has been released showing just how effective the Johnson & Johnson is at protecting against the Delta variant, though it is believed that the single-shot vaccine does offer protection against the variant. Dr. Scott Gottlieb, former Food and Drug Administration commissioner, reportedly said the Johnson & Johnson vaccine appears to be about 60% effective against the Delta variant. Still, medical experts say any of the three vaccines currently being used in the U.S. continue to show good results as far as protection. ”This will protect them against getting very sick and being hospitalized and even dying from the Delta variant,” Dr. Katherine Gergen-Barnett of Boston Medical Center recently told NBC10 Boston.

Will a booster shot be needed?

So far, there has been no recommendation from the Centers for Disease Control and Prevention surrounding booster shots with the Delta variant. Still, health experts have repeatedly cautioned that COVID-19 booster shots could be needed for fully vaccinated people, particularly as new variants spread. White House chief advisor Dr. Anthony Fauci said during an interview with MSNBC's Medhi Hasan in April that people may need to get booster shots in a year.  Pfizer CEO Albert Bourla also previously said people will "likely" need a third dose within 12 months of getting fully vaccinated.  So far, studies suggest that the vaccines currently in use can recognize the emerging variants — but they may not provide quite as much protection against the new strains. Boosters and new versions of vaccines that target the variants are already being explored. Pfizer-BioNTech was previously testing a third booster shot of its vaccine on fully vaccinated people.   "The flexibility of our proprietary mRNA vaccine platform allows us to technically develop booster vaccines within weeks, if needed," Sahin said in a release in February. Moderna was also testing a potential third dose of its current vaccine, and a possible booster shot specifically targeting the South Africa variant. Citing early data, the company recently said the booster vaccine generated a promising immune response against the B.1.351 and P.1 variants first identified in South Africa and Brazil, respectively. Meanwhile, Johnson & Johnson CEO Alex Gorsky said during an interview with CNBC's "Squawk Box" in March that the company is well-positioned to adapt its vaccine for variants, and is working on developing software that will "help address some of these new and emerging variants."

Data have demonstrated vaccine protects against COVID-19 related hospitalization in broad geographic regions, including those with emerging variants. Decision follows the European Medicines Agency recommendation of the J&J COVID-19 vaccine. The Company aims to begin delivery of its vaccine to the EU in the second half of April and is committed to supply 200 million doses in 2021. 

NEW BRUNSWICK, N.J., March 11, 2021 – Johnson & Johnson (NYSE: JNJ) (the Company) today announced that the European Commission (EC) has granted a Conditional Marketing Authorization (CMA) for its single-dose COVID-19 vaccine, developed by the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), to prevent COVID-19 in individuals 18 years of age and older. The CMA follows a Positive Opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The CMA is valid in all 27 member states of the European Union (EU), plus Norway, Iceland and Liechtenstein. Data from the Phase 3 ENSEMBLE study showed that the Johnson & Johnson COVID-19 vaccine was well tolerated and demonstrated a 67 percent reduction in symptomatic COVID-19 disease in participants who received the vaccine in comparison to participants given the placebo. The onset of protection was observed from day 14 and was maintained 28 days post-vaccination.1 The data also demonstrated the vaccine was 85 percent effective in preventing severe disease across all regions studied, and showed protection against COVID-19 related hospitalisation and death, beginning 28 days after vaccination.

“For more than a year, we have been working around the clock – leveraging the scientific minds, scale and resources of our global organisation to bring forward a COVID-19 vaccine,” said Alex Gorsky, Chairman and Chief Executive Officer at Johnson & Johnson. “We are thrilled with today’s Conditional Marketing Authorization by the European Commission, which enables our single-dose vaccine to reach many more communities in need, as we continue to do everything we can to help bring an end to this pandemic.” Johnson & Johnson is committed to making its COVID-19 vaccine available on a not-for-profit basis for emergency pandemic use. The Company aims to begin delivery of its single dose COVID-19 vaccine to the EU in the second half of April and to supply 200 million doses to the EU, plus Norway and Iceland in 2021. “This vaccine is the result of more than a decade of investment in research and development and deep commitment by our scientists. We appreciate the collaboration and the support of the European Commission in this monumental effort,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer at Johnson & Johnson. “With this Conditional Marketing Authorization, we are proud to bring our single-shot vaccine to help protect millions of people across EU member states.”

In December 2020, the Company announced that Janssen initiated a rolling submission with the EMA for its single-dose COVID-19 vaccine candidate, enabling an expedited CHMP review process. The COVID-19 vaccine candidate has also been filed for an Emergency Use Listing (EUL) with the World Health Organization. Rolling submissions for our vaccine candidate have also been initiated in several countries worldwide. “This latest major regulatory milestone would not have been possible without the hard work and dedication of everyone involved in our COVID-19 vaccine clinical trial programme, including our J&J team, our partners and study participants,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “We are delighted by today’s announcement and remain fully committed to continuing our COVID-19 vaccine clinical programme as we strive to provide our single-dose COVID-19 vaccine to people all over the world.” The Company received Emergency Use Authorization (EUA) in the United States on February 27, following a unanimous vote by the U.S. Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee on February 26, 2021. The Johnson & Johnson single-dose COVID-19 vaccine has also been granted Interim Order authorisation in Canada.

EMA Press Release (March 11, 2021):

https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-janssen-authorisation-eu 

The J&J vaccine could be a game changer, at least in some areas, because it does not need to be frozen and requires only a single dose. An advisory panel on Friday recommended the Food and Drug Administration grant an emergency use authorization for Johnson & Johnson’s Covid-19 vaccine developed by Johnson & Johnson, which would become the third vaccine authorized in the United States and the first to require a single shot. In a statement issued shortly after the vote, the FDA said it has told the company regulators “will rapidly work toward finalization and issuance of an emergency use authorization.” The agency also said it has notified federal partners involved in vaccine distribution “so they can execute their plans for timely vaccine distribution.” Authorization of J&J’s vaccine could be a potential game changer, at least in some areas. Made by J&J’s vaccine division, Janssen Pharmaceuticals, the single-dose vaccine does not need to be frozen when it is shipped and distributed. The vaccine is what’s known as “fridge stable,” meaning it can be shipped and stored at the temperature of a regular refrigerator. Both those characteristics will make this vaccine much easier to deploy if the FDA authorizes its use. The two vaccines already in use in the United States, from Moderna and the Pfizer-BioNTech partnership, are both two-dose vaccines with onerous cold-chain requirements.  Although the FDA does not have to follow the recommendation of the panel, known as the Vaccines and Related Biological Products Advisory Committee or VRBPAC, it is widely expected to do so. The J&J vaccine hasn’t been tested yet in children and teens under the age of 18, so it will not be authorized for use in them.

The J&J vaccine was found to reduce cases of moderate to severe Covid infection by 66.1%, starting 28 days after the single shot. (It takes a while for the protection of the vaccine to build up.) Results released in late January suggested the vaccine worked better in some areas than others; in the U.S., the vaccine was 72% protective. An FDA analysis of the J&J data, released on Wednesday, suggested the vaccine was a little less effective against a virus variant first spotted in South Africa, known as B.1.351. But its protection did not appear to be eroded by a variant first spotted in Brazil, known as P.2. The United States has purchased 100 million doses of the J&J vaccine, but supplies are expected to be scarce until at least April. STAT’s coverage of the meeting is below, with updates and analysis posted in reverse chronological order....

FDA materials evaluated by he VRBPAC panel (Feb. 26, 2021):

https://www.fda.gov/media/146217/download 

“We should be reassured by the care taken by independent regulators to protect the public," AstraZeneca's CEO said. Two major studies of vaccines against Covid-19, both paused because of potential safety concerns, are set to restart, the companies running them said Friday. “The restart of clinical trials across the world is great news as it allows us to continue our efforts to develop this vaccine to help defeat this terrible pandemic,” Pascal Soriot, AstraZeneca’s CEO, said in a statement. “We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.” “We as a company have found no evidence the vaccine candidate caused the event, and we have agreed to restart the study,” Paul Stoffels, the chief scientific officer at Johnson & Johnson, said in an interview. In both cases, new documents describing potential risks for both researchers and volunteers have been prepared, and must be approved by a centralized institutional review board, one of several groups charged with protecting patients in the trial.

AstraZeneca’s restart was first reported by the Wall Street Journal; the impending restart of the J&J study was first reported by the Washington Post.  AstraZeneca stopped administering new doses of its vaccine on Sept. 6, a step first reported by STAT, after a participant in the trial developed neurological symptoms. These symptoms were reportedly caused by transverse myelitis, a serious spinal cord condition.  AstraZeneca said in its statement that the voluntary pause was part of its standard review process for safety events, and that such pauses are not unusual. It said reviews from the trial’s independent monitoring  committees indicated it was safe for the trials to resume, and that this conclusion was supported by international regulators.  A study of the vaccine in the U.K. restarted on Sept. 12, and shortly thereafter studies in Brazil and South Africa resumed. A study in Japan restarted earlier this month. But the Food and Drug Administration decided to further investigate the case, and the U.S. trial has remained on hold for more than a month.

A trial of another vaccine, being developed by Johnson & Johnson, was paused on Oct. 11.  According to a person familiar with the matter, a male volunteer in his twenties had a cerebral hemorrhage and transverse sinus venous thrombosis. The Washington Post, citing two sources, said this case was a stroke. Stoffels said that the case was reviewed by external experts, with reports made continuously both by the study’s data and safety monitoring board, an outside panel overseeing the studies, and the FDA. A final report was sent to the agency late this week. Circumstances with the patient made the process slower than it might have been. “We worked as hard as we could,” Stoffels said. “We would not put more people at risk until we knew what the cause or relationship would be.” The J&J study could begin enrolling patients again early next week, Stoffels said. He noted that the study already includes a large number of sites, and that the company will be making sure the participants are diverse in their ethnic background, their age, and any disorders they have that could make them higher risk. The J&J effort is important because it is the only one of the major vaccine efforts to be testing a single dose, and the company has made the main goal of its study to test whether the vaccine prevents severe or moderate Covid-19, not just symptomatic cases of the disease.

(Reuters) - GlaxoSmithKline Plc said an injection of its cabotegravir drug given every two months, in combination with Johnson & Johnson’s rilpivirine, was recommended for approval to treat HIV infections by a panel of the European health regulator. The treatment is a long-acting regimen, which can reduce the number of doses required to 12 or six per year instead of a daily intake of pills. If approved, it would be the first complete long-acting HIV regimen requiring dosing just once in two months (in the EU region), GSK said. The combination as an injection is already approved in Canada and is currently under review in the United States. Shares of GSK were trading up 2.5% at 1410.4p, while J&J shares were marginally up during premarket trading. Gilead’s Truvada daily oral pill is currently the standard of care for preventing HIV, but GSK hopes to challenge its dominance by making shorter, long-lasting regimens and less toxic alternatives through its ViiV Healthcare unit.

The positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency comes months after GSK said cabotegravir was found to be 66% more effective in preventing HIV infections than Truvada. Some 75 million people worldwide have been infected with HIV and about 32 million people have died since it began in the 1980s. While final approvals are up to the European Commission, it generally follows the CHMP’s recommendation and endorses them within a couple of months.

GSK public announcement (Oct. 16, 2020):

https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-receives-positive-chmp-opinion-for-long-acting-regimen-for-the-treatment-of-hiv/

Early results from a Phase 1/2a clinical trial shows it was well tolerated and even one dose appeared to produce a strong immune response in almost all of the 800 participants.  There is some good news on Johnson & Johnson's coronavirus vaccine.. The trial included two age groups: 18- to 55-year-olds and 65 and older, and looked at the safety and side effects of two different doses. Initial findings from the trials suggest the vaccine does provoke an immune response and is safe enough to move into large-scale trials. The study was posted on MedRxiv, but it has not been peer-reviewed or published in a medical journal yet. The researchers found that 99% of the participants age 18 to 55 in both dose groups had developed antibodies against the virus 29 days after getting vaccinated. The analysis found that most of the side effects, like fever, headache, fatigue, body aches and injection-site pain, were mild and resolved after a couple of days. Some of the participants will be receiving a second shot of the vaccine as part of the trial. The vaccine -- called Ad26.COV2.S -- uses the same technology used for Johnson & Johnson's Ebola, Zika, HIV and RSV vaccines.

Adenovirus vectors deliver the genetic instructions for SARS-CoV-2 antigens directly into patients' cells, provoking a robust immune response. But will pre-existing immunity from common colds take them down?  Six vaccine candidates in clinical trials for COVID-19 employ viruses to deliver genetic cargo that, once inside our cells, instructs them to make SARS-CoV-2 protein. This stimulates an immune response that ideally would protect recipients from future encounters with the actual virus. Three candidates rely on weakened human adenoviruses to deliver the recipe for the spike protein of the pandemic coronavirus, while two use primate adenoviruses and one uses measles virus. Most viral vaccines are based on attenuated or inactivated viruses. An upside of using vectored vaccines is that they are easy and relatively cheap to make. The adenovirus vector, for example, can be grown up in cells and used for various vaccines. Once you make a viral vector, it is the same for all vaccines, says Florian Krammer, a vaccinologist at the Icahn School of Medicine at Mount Sinai. “It is just the genetic information in it that is different,” he explains. Once inside a cell, viral vectors hack into the same molecular system as SARS-CoV-2 and faithfully produce the spike protein in its three dimensions. This resembles a natural infection, which provokes a robust innate immune response, triggering inflammation and mustering B and T cells. But the major downside to the human adenoviruses is that they circulate widely, causing the common cold, and some people harbor antibodies that will target the vaccine, making it ineffective.

CanSino reported on its Phase II trial this summer of its COVID-19 vaccine that uses adenovirus serotype 5 (Ad5). The company noted that 266 of the 508 participants given the shot had high pre-existing immunity to the Ad5 vector, and that older participants had a significantly lower immune response to the vaccine, suggesting that the vaccine will not work so well in them. “The problem with adenovirus vectors is that different populations will have different levels of immunity, and different age groups will have different levels of immunity,” says Nikolai Petrovsky, a vaccine researcher at Flinders University in Australia. Also, with age, a person accumulates immunity to more serotypes. “Being older is associated with more chance to acquire Ad5 immunity, so those vaccines will be an issue [with elderly people],” Krammer explains. Moreover, immunity against adenoviruses lasts for many years. “A lot of people have immunity to Ad5 and that impacts on how well the vaccine works,” says Krammer. In the US, around 40 percent of people have neutralizing antibodies to Ad5. As part of her work on an HIV vaccine, Hildegund Ertl of the Wistar Institute in Philadelphia previously collected serum in Africa to gauge resistance levels to this and other serotypes. She found a high prevalence of Ad5 antibodies in sub-Saharan Africa and some West African countries—80 to 90 percent. A different group in 2012 reported that for children in northeast China, around one-quarter had moderate levels and 9 percent had high levels of Ad5 antibodies.  “I don’t think anyone has done an extensive enough study to do a world map [of seroprevalence],” notes Ertl. 

J&J’s Janssen is using a rarer adenovirus subtype, Ad26, in its COVID-19 vaccine, reporting in July that it protects macaques against SARS-CoV-2 and in September that it protects against severe clinical disease in hamsters. Ad26 neutralizing antibodies are uncommon in Europe and the US, with perhaps 10–20 percent of people harboring antibodies. They are more common elsewhere. “In sub-Saharan Africa, the rates are ranging from eighty to ninety percent,” says Ertl. Also critical is the level of antibodies in individuals, notes Dan Barouch, a vaccinologist at Beth Israel Deaconess Medical Center and Harvard Medical School. For instance, there was no neutralizing of Ad26-based HIV and Ebola vaccines in more than 80,000 people in sub-Saharan Africa, he says. “Ad26 vaccine responses do not appear to be suppressed by the baseline Ad26 antibodies found in these populations,” because the titres are low, Barouch writes in an email to The Scientist. Barouch has long experience with Ad26-based vaccines and collaborates with J&J on their COVID-19 vaccine. The Russian Sputnik V vaccine, approved despite no published data or Phase 3 trial results, starts with a shot of Ad26 vector followed by a booster with Ad5, both of which carry the gene for the spike protein of SARS-CoV-2. This circumvents a downside of viral vector vaccines, specifically, once you give the first shot, subsequent injections will be less efficacious because of antibodies against the vector. Ertl says she has no idea of the proportion of the Russian population with Ad26 or Ad5 antibodies, and there seems to be little or no published data from countries that have expressed interested in this virus, such as Venezuela and the Philippines...