Virus World

Today, the U.S. Food and Drug Administration authorized a second booster dose of either the Pfizer-BioNTech or the Moderna COVID-19 vaccines for older people and certain immunocompromised individuals. The FDA previously authorized a single booster dose for certain immunocompromised individuals following completion of a three-dose primary vaccination series. This action will now make a second booster dose of these vaccines available to other populations at higher risk for severe disease, hospitalization and death. Emerging evidence suggests that a second booster dose of an mRNA COVID-19 vaccine improves protection against severe COVID-19 and is not associated with new safety concerns. The agency amended the emergency use authorizations as follows: 

• A second booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine may be administered to individuals 50 years of age and older at least 4 months after receipt of a first booster dose of any authorized or approved COVID-19 vaccine.
• A second booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be administered to individuals 12 years of age and older with certain kinds of immunocompromise at least 4 months after receipt of a first booster dose of any authorized or approved COVID-19 vaccine. These are people who have undergone solid organ transplantation, or who are living with conditions that are considered to have an equivalent level of immunocompromise.
• A second booster dose of the Moderna COVID-19 Vaccine may be administered at least 4 months after the first booster dose of any authorized or approved COVID-19 vaccine to individuals 18 years of age and older with the same certain kinds of immunocompromise.

“Current evidence suggests some waning of protection over time against serious outcomes from COVID-19 in older and immunocompromised individuals. Based on an analysis of emerging data, a second booster dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine could help increase protection levels for these higher-risk individuals,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Additionally, the data show that an initial booster dose is critical in helping to protect all adults from the potentially severe outcomes of COVID-19. So, those who have not received their initial booster dose are strongly encouraged to do so.”

Today’s action applies only to the Pfizer-BioNTech and Moderna COVID-19 vaccines and the authorization of a single booster dose for other age groups with these vaccines remains unchanged. The agency will continue to evaluate data and information as it becomes available when considering the potential use of a second booster dose in other age groups.  The FDA-authorized Pfizer-BioNTech COVID-19 Vaccine and the FDA-approved Comirnaty can be used to provide the authorized booster dose(s). Similarly, the FDA-authorized Moderna COVID-19 Vaccine and the FDA-approved Spikevax are authorized to provide the authorized booster dose(s).

Information to Support Authorization of a Second COVID-19 Booster Dose

The FDA has determined that the known and potential benefits of a second COVID-19 vaccine booster dose with either of these vaccines outweigh their known and potential risks in these populations. The evidence considered for authorization of a second booster dose following primary vaccination and first booster dose included safety and immune response information provided to the agency as well as additional information on effectiveness submitted by the companies.  A summary of safety surveillance data provided to the FDA by the Ministry of Health of Israel on the administration of approximately 700,000 fourth (second booster) doses of the Pfizer-BioNTech COVID-19 Vaccine given at least 4 months after the third dose in adults 18 years of age and older (approximately 600,000 of whom were 60 years of age or older) revealed no new safety concerns.  The safety of Moderna COVID-19 Vaccine, when administered as a second booster dose, is informed by experience with the Pfizer-BioNTech COVID-19 Vaccine and safety information reported from an independently conducted study in which the Moderna COVID-19 Vaccine was administered as a second booster dose to 120 participants 18 years of age and older who had received a two-dose primary series and a first booster dose of Pfizer-BioNTech COVID-19 Vaccine at least 4 months prior.

No new safety concerns were reported during up to three weeks of follow up after the second booster dose. Immunogenicity data from an ongoing, open-label, non-randomized clinical study in healthcare workers at a single center in Israel were reported in a publication provided to the FDA. In this study, individuals 18 years of age and older who had received primary vaccination and a first booster dose with Pfizer-BioNTech COVID-19 Vaccine were administered a second booster dose of Pfizer-BioNTech COVID-19 Vaccine (154 individuals) or Moderna COVID-19 Vaccine (120 individuals) at least four months after the first booster dose. Among these individuals, increases in neutralizing antibody levels against SARS-CoV-2 virus, including delta and omicron variants were reported two weeks after the second booster as compared to 5 months after the first booster dose. The amendments to the EUAs to include a second booster dose for these populations were granted to Pfizer Inc. and ModernaTX Inc.

Moderna’s coronavirus vaccine could potentially induce as strong an immune response in older people as it does in younger adults, a small study published Tuesday in the New England Journal of Medicine found. The study found the vaccine triggered a response almost as strong in people over 56 as in adults between the ages of 18 and 55. Older people are at higher risk for severe illness from COVID-19, according to the Centers for Disease Control and Prevention. The Moderna study was conducted by researchers at Emory University and tested the vaccine in groups of 20 people, including one made up of people aged 56-70 and one of people 71 and over. According to the study, their response was similar to previous findings among age groups between 18-55. 

“These interim results are very encouraging,” Evan Anderson, a professor of infectious disease at Emory University Medical School and lead author on the paper, said in a statement. “While there is still a lot of work to do before we have a vaccine that is proven to be safe and effective against COVID-19, this study provides critical information about the safety of the vaccine. Importantly, the vaccine resulted in a robust immune response. Moderna is one of a handful of companies working on a vaccine and is now in phase three clinical trials in the United States. 

The biotech company’s small preliminary study indicates the vaccine produced similar levels of antibodies for younger people and those aged 56 and older. Massachusetts-based biotech company Moderna said Wednesday that in a small trial, its experimental coronavirus vaccine produced a similar number of antibodies for people aged 56 years and older as younger adults in a preliminary study, a promising sign for the high-risk age group amid concern that vaccines wouldn’t offer as much protection for older adults. Older adults are at higher risk of hospitalization and death from Covid-19 than younger people and, because the immune system usually weakens with age, it can be harder for a vaccine to be effective, according to the U.S. Centers for Disease Control and Prevention. Moderna, which reported in July that its vaccine induced immune response and was generally safe and well tolerated in adults aged 18 to 55, said during a presentation to medical experts and advisors that it had expanded its study to a small group of older adults. Moderna tested its vaccine on 10 adults between the ages of 56 and 70 and 10 adults aged 71 and older and found that the older volunteers developed antibodies in a similar range as the younger volunteers; Moderna said the vaccine was well-tolerated with no serious side effects reported. Moderna presented the data, which has yet to be peer reviewed, Wednesday to a committee of outside experts to advise the U.S. Centers for Disease Control and Prevention on vaccine practices.

Earlier this month, President Trump said the U.S. government will purchase 100 million doses of Moderna’s coronavirus vaccine candidate for $1.5 billion as part of Operation Warp Speed which hopes to find at least one safe, effective vaccine by the end of the year. The goal of the federal government’s Operation Warp Speed initiative is to spur the production of promising vaccine candidates and to buy initial batches so they can be distributed as soon as a candidate is approved. The White House has made similar deals over the last few months with other companies developing vaccines, including Johnson & Johnson, Pfizer, Novavax, AstraZeneca and GlaxoSmithKline and Sanofi. The U.S. had already given $955 million to help Moderna research develop its vaccine through the Biomedical Advanced Research and Development Authority. Although a vaccine might be proven safe and effective by early next year, Dr. Anthony Fauci said last month he doesn’t anticipate widespread availability with hundreds of millions of doses until “several months” into 2021. $2.1 billion. That’s Moderna CEO Stéphane Bancel’s net worth, according to Forbes estimates. He became a billionaire in April as Moderna stock jumped after announcing it expected to begin Phase 2 human trials for its Covid-19 vaccine.

Data on past trials raises concerns for University of Massachusetts and Mt Sinai researchers that COVID-19 drugs and vaccines won't be tested in people over 65, who need them most. Americans over 65 were excluded from half of all US clinical trials of drugs and all trials for vaccines - including those for COVID-19 - from October of last year until June 1, 2020, new research reveals. People over 65 are the most likely to develop severe COVID-19 and die of the devastating viral infection.  Yet they have been systematically left behind 50 percent of the time as scientists tried experimental therapies in trials of drugs for any condition, including those for coronavirus, like remdesivir, which might have saved the lives of thousands of older Americans. 

Older people were left out of 100 percent despite the fact that they will likely be the first Americans to receive a shot once one is FDA-approved - far ahead of the young people  vaccines were tested in.  In ordinary circumstances, older people face higher risks of complications if they are enrolled in trials of experimental drugs and vaccines, so they may be excluded. But in the unprecedented scenario of the COVID-19 pandemic, researchers at University of Massachusetts and the Icahn School of Medicine at Mount Sinai worry  that the risks of giving older people treatments and shots with unknown effects may outweigh those of testing them in clinical settings. 'To be sure, some exclusions are needed to protect the health and safety of older adults - such as poorly controlled comorbidities,' said senior study author Dr Sharon Inouye, director of the  Brain Aging Center at Hebrew SeniorLife, at the University of Massachusetts. However, many [exclusions] are not well-justified, and appear to be more for expediency or convenience of the trialists.' People over 65 account for just nine percent of the global population, but more than 80 percent of COVID-19 deaths thus far have been people in this older age group.  

Although the first case of coronavirus in the US was not identified until late January 2020, the researchers looked at 847 trials registered to ClinicalTrials.gov from October 1, 2019 until June 1, 2020.  Of the trials, 23 percent had age cut-offs. The trials primarily cited concerns that older enrollees would not comply with treatment of vaccine regimens. Others wrote they believed it would be too difficult to get informed consent from older participants.  The researchers then combined the number of studies that explicitly excluded older Americans and those that had other exclusions likely to make the inaccessible to older adults.  In total, 53 percent of all drug trials were likely to have very low or no enrollment of adults over 65.  And 100 percent of vaccine trials were estimated to exclude older adults.  As a consequence of the time period, most trials included in the study were not for COVID-19 drugs and vaccines specifically.  But, 'our concern is more than theoretical,' the study authors wrote.  'Even without stated age-based exclusions, several recently published clinical trials of COVID-19 treatments had young age ranges, such as one recent study with a median age of only 40 years, meaning there would be no or few participants over age 75. If the older age group is excluded from vaccine trials, efforts to ensure effectiveness, titrate dosage or frequency, and assess adverse effects in the group most vulnerable to COVID-19 will not be possible.'...

Study cited published in JAMA (Sept. 28, 2020):

https://doi.org/10.1001/jamainternmed.2020.5084