Posted on by Dr. Francis Collins
The winter holidays are approaching, and among the many things to be grateful for this year is that nearly 200 million Americans are fully vaccinated for COVID-19. That will make it safer to spend time with friends and family, though everyone should remain vigilant just to be on the safe side. Though relatively uncommon, breakthrough infections are possible. That’s why the Centers for Disease Control and Prevention (CDC) recommends booster shots for several at-risk groups, including folks 65 years and older, those with underlying medical conditions, and people whose occupations place them at high risk of exposure.
One of the main studies providing the evidence for CDC’s recommendation was recently published in the New England Journal of Medicine . It found that vaccine-induced immunity, while still quite protective against infection and severe illness from COVID-19, can wane after several months.
The study is yet another highly informative report from Israel, where public health officials launched a particularly vigorous national vaccination campaign in December 2020. More than half of adult Israelis received two doses of the Pfizer vaccine within the first three months of the campaign. By May 2021, Israel had extremely small numbers of confirmed COVID-19 cases—just a few dozen per day.
But the numbers crept back up in June 2021. The rise also included a substantial number of breakthrough infections in vaccinated individuals. The vast majority of those cases in June—98 percent—were caused by the emerging Delta variant.
Researchers led by Yair Goldberg, Technion-Israel Institute of Technology, Haifa, wondered whether this resurgence of COVID-19 could be fully explained by the rise of the more infectious Delta variant. Or, they wondered, did the waning of immunity over time also play a role?
To find out, the researchers looked to over 4.7 million fully vaccinated Israeli adults, more than 13,000 of whom had breakthrough infections from July 11 to 31, 2021 with SARS-CoV-2. The researchers looked for an association between the rate of confirmed infections and the time that had passed since vaccination. Without any significant waning of immunity, one shouldn’t see any difference in infection rates among people who were fully vaccinated at the earliest opportunity versus those vaccinated later.
The results were clear: the rate of confirmed COVID-19 infection revealed a slow but steady waning of immunity over time. Among individuals 60 years or older who were fully vaccinated last January, the number of confirmed breakthrough infections was 3.3 per 1,000 people during the three weeks of the study. Those who were vaccinated in February and March had lower infection rates of 2.2 per 1,000 and 1.7 per 1,000, respectively. The data revealed a similar pattern in those aged 40 to 59 and those aged 16 to 39.
An important question is whether these breakthrough infections were serious enough to require hospitalization. While such cases were much less common, more than 400 of those with confirmed COVID-19 breakthroughs went on to develop severe illness. And, again, the data show a similar pattern of waning immunity. The rate of severe COVID-19 among adults 60 years of age or older who were fully vaccinated in January was 0.34 cases per 1,000 persons. The rate of severe illness dropped to 0.26 cases per 1,000 among those vaccinated in February and 0.15 cases per 1,000 for those vaccinated in March. The researchers report that the number of severe COVID-19 cases among the younger fully vaccinated groups were too small to draw any conclusions.
While the Delta variant surely has played a role in the resurgence of COVID-19 in recent months, these findings suggest that waning immunity also is an important factor. Understanding these dynamics is essential for making critical policy decisions. In fact, these data were a key factor in the decision by the Israeli Ministry of Health in July 2021 to approve administration of COVID-19 booster shots for individuals who’d been vaccinated at least 5 months before.
Back in the U.S., if you were among those who got your vaccine on the early side—good for you. If it’s been more than six months since your original shots, and if you are in one of the risk groups, you should consider a COVID-19 booster shot to remain optimally protected in the months ahead. I’ll be getting my Moderna booster this week. While you’re at it, consider getting your annual flu shot taken care of, too. The CDC guidelines state that it’s perfectly OK to get your COVID-19 and flu shots at the same time.
 Waning immunity after the BNT162b2 vaccine in Israel. Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman L, Haas EJ, Milo R, Alroy-Preis S, Ash N, Huppert A. N Engl J Med. 2021 Oct 27.
COVID-19 Research (NIH)
COVID-19 Vaccine Booster Shots (Centers for Disease Control and Prevention)
COVID-19 Vaccine Appears Well-Tolerated and Effective in Developing Antibodies in Small Study of Older Adults
Posted on by Dr. Francis Collins
It’s been truly breathtaking to watch the progress being made on a daily basis to develop safe and effective vaccines for SARS-CoV-2, the novel coronavirus that causes COVID-19. Indeed, months sooner than has ever been possible for a newly emerging infection, several promising vaccines are already working their way through Phase 3 studies, the final stage of clinical evaluation. I remain optimistic that we will have one or more vaccines that prove to be safe and effective by January 2021.
But, as encouraging as the early data have been, uncertainty has remained over whether vaccines that appear safe and effective in developing antibodies in younger adults will work as well in older people, too. It’s a critical issue given that older individuals also are at greater risk for severe or life-threatening illness if they do get sick from COVID-19.
So, I’m pleased to highlight some recent findings, published in the New England Journal of Medicine , from an early Phase 1 clinical trial that was expanded to include 40 adults over age 55. While we eagerly await the results of ongoing and larger studies, these early data suggest that an innovative COVID-19 vaccine co-developed by NIH’s Vaccine Research Center (VRC), in partnership with Moderna Inc., Cambridge, MA, is both well tolerated and effective in generating a strong immune response when given to adults of any age.
The centerpiece of the vaccine in question, known as mRNA-1273, is a small, non-infectious snippet of messenger RNA (mRNA). When this mRNA is injected into muscle, a person’s own body will begin to make the key viral spike protein. As the immune system detects this spike protein, it spurs the production of antibodies that may help to fend off the novel SARS-CoV-2.
Earlier findings from the NIH-supported phase 1 human clinical trial found mRNA-1273 was safe and effective in generating a vigorous immune response in people ages 18 to 55, when delivered in two injections about a month apart. Based on those findings, a large Phase 3 clinical trial is currently enrolling 30,000 volunteers, with results expected in the next few weeks . But, given that immune response to many other vaccines tends to grow weaker with age, how well would this new COVID-19 vaccine work for older individuals?
To find out, a team at Kaiser Permanente Washington Health Research Institute, Seattle, and Emory University School of Medicine, Atlanta, expanded the initial Phase 1 trial to include 20 healthy volunteers ages 56 to 70 and another 20 healthy volunteers ages 71 and older. Ten volunteers in each of the two older age groups received a lower dose of the vaccine (25 micrograms) in two injections given about a month apart. The other 10 in each age group received a higher dose (100 micrograms), given on the same schedule.
Here’s what they found:
• No volunteers suffered serious adverse events. The most common adverse events were mild-to-moderate in severity and included headache, fatigue, muscle aches, chills and pain at the injection site. Those symptoms occurred most often after the second dose and in individuals receiving the higher dose of 100 micrograms.
• Volunteers showed a rapid production of protective antibodies against the spike protein following immunization. After the second injection, all participants showed a strong immune response, with production of robust binding and neutralizing antibodies against SARS-CoV-2.
• The higher dose of 100 micrograms safely produced a stronger immune response compared to the lower dose, supporting its use in larger clinical studies.
• Most importantly, the immune response observed in these older individuals was comparable to that seen previously in younger adults.
The researchers will continue to follow the volunteer trial participants of all ages for about a year to monitor the vaccine’s longer-term effects. But these findings provided support for continued testing of this promising vaccine in older adults in the ongoing Phase 3 clinical trial.
There are currently four SARS-CoV-2 vaccines in phase 3 clinical trials in the United States (though two are currently on hold). Trials of two more vaccines are expected start in the next month or two.
It is not known whether all of these vaccines will have the same vigorous immune response in older individuals that has been demonstrated for this one. But if more than one of these vaccines turns out to be safe and effective, it will be important to know about the response in various populations, so that distribution to high-risk groups can be planned accordingly.
 Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott AB, Flach B, Lin BC, Doria-Rose NA, O’Dell S, Schmidt SD, Corbett KS, Swanson PA 2nd, Padilla M, Neuzil KM, Bennett H, Leav B, Makowski M, Albert J, Cross K, Edara VV, Floyd K, Suthar MS, Martinez DR, Baric R, Buchanan W, Luke CJ, Phadke VK, Rostad CA, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. N Engl J Med. 2020 Sep 29.
 “Phase 3 clinical trial of investigational vaccine for COVID-19 begins.” National Institutes of Heath. July 27, 2020
Coronavirus (COVID-19) (NIH)
COVID-19 Prevention Network (National Institute of Allergy and Infectious Diseases/NIH)
Dale and Betty Bumpers Vaccine Research Center (National Institute of Allergy and Infectious Diseases/NIH)
Moderna, Inc. (Cambridge, MA)
NIH Support: National Institute of Allergy and Infectious Diseases