Posted on by Lawrence Tabak, D.D.S., Ph.D.
As colder temperatures settle in and people spend more time gathered indoors, cases of COVID-19 and other respiratory illnesses almost certainly will rise. That’s why, along with scheduling your annual flu shot, it’s now recommended that those age 5 and up should get an updated COVID-19 booster shot [1,2]. Not only will these new boosters guard against the original strain of the coronavirus that started the pandemic, they will heighten your immunity to the Omicron variant and several of the subvariants that continue to circulate in the U.S. with devastating effects.
At last count, about 14.8 million people in the U.S.—including me—have rolled up their sleeves to receive an updated booster shot . It’s a good start, but it also means that most Americans aren’t fully up to date on their COVID-19 vaccines. If you or your loved ones are among them, a new study may provide some needed encouragement to make an appointment at a nearby pharmacy or clinic to get boosted .
A team of NIH-supported researchers found a remarkably low incidence of severe COVID-19 illness last fall, winter, and spring among more than 1.6 million veterans who’d been vaccinated and boosted. Severe illness was also quite low in individuals without immune-compromising conditions.
These latest findings, published in the journal JAMA, come from a research group led by Dan Kelly, University of California, San Francisco. He and his team conducted their study drawing on existing health data from the Veterans Health Administration (VA) within a time window of July 2021 and May 2022.
They identified 1.6 million people who’d had a primary-care visit within the last two years and were fully vaccinated for COVID-19, which included receiving a booster shot. Almost three-quarters of those identified were 65 and older. Nearly all were male, and more than 70 percent had another pre-existing health condition that put them at greater risk of becoming seriously ill from a COVID-19 infection.
Over a 24-week follow-up period for each fully vaccinated individual, 125 per 10,000 people had a breakthrough infection. That’s about 1 percent. Just 8.9 in 10,000 fully vaccinated people—less than 0.1 percent—died or were hospitalized from COVID-19 pneumonia. Drilling down deeper into the data:
• Individuals with an immune-compromising condition had a very low rate of hospitalization or death. In this group, 39.6 per 10,000 people had a serious breakthrough infection. That translates to 0.3 percent.
• For people with other preexisting health conditions, including diabetes and heart disease, hospitalization or death totaled 0.07 percent, or 6.7 per 10,000 people.
• For otherwise healthy adults aged 65 and older, the incidence of hospitalization or death was 1.9 per 10,000 people, or 0.02 percent.
• For boosted participants 65 or younger with no high-risk conditions, hospitalization or death came to less than 1 per 10,000 people. That comes to less than 0.01 percent.
It’s worth noting that these results reflect a period when the Delta and Omicron variants were circulating, and available boosters still were based solely on the original variant. Heading into this winter, the hope is that the updated “bivalent” boosters from Pfizer and Moderna will offer even broader protection as this terrible virus continues to evolve.
The Centers for Disease Control and Prevention continues to recommend that everyone stay up to date with their COVID-19 vaccines. That means all adults and kids 5 and older are encouraged to get boosted if it has been at least two months since their last COVID-19 vaccine dose. For older people and those with other health conditions, it’s even more important given their elevated risk for severe illness.
What if you’ve had a COVID-19 infection recently? Getting vaccinated or boosted a few months after you’ve had a COVID-19 infection will offer you even better protection in the future.
So, if you are among the millions of Americans who’ve been vaccinated for COVID-19 but are now due for a booster, don’t delay. Get yourself boosted to protect your own health and the health of your loved ones as the holidays approach.
 CDC recommends the first updated COVID-19 booster. Centers for Disease Control and Prevention. September 1, 2022.
 CDC expands updated COVID-19 vaccines to include children ages 5 through 11. Centers for Disease Control and Prevention, October 12, 2022.
 COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention.
 Incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, Lum EN, Moss-Vazquez TA, Andino R, Wong JK, Byers A, Bravata DM, Tien PC, Keyhani S. JAMA. 2022 Oct 11;328(14):1427-1437.
COVID-19 Research (NIH)
Dan Kelly (University of California, San Francisco)
NIH Support: National Institute of Allergy and Infectious Diseases
Posted on by Lawrence Tabak, D.D.S., Ph.D.
More than 215 million people in the United States are now fully vaccinated against the SARS-CoV-2 virus responsible for COVID-19 . More than 40 percent—more than 94 million people—also have rolled up their sleeves for an additional, booster dose. Now, an NIH-funded study exploring how mRNA vaccines are performing over time comes as a reminder of just how important it will be to keep those COVID-19 vaccines up to date as coronavirus variants continue to circulate.
The results, published in the journal Science Translational Medicine, show that people who received two doses of either the Pfizer or Moderna COVID-19 mRNA vaccines did generate needed virus-neutralizing antibodies . But levels of those antibodies dropped considerably after six months, suggesting declining immunity over time.
The data also reveal that study participants had much reduced protection against newer SARS-CoV-2 variants, including Delta and Omicron. While antibody protection remained stronger in people who’d also had a breakthrough infection, even that didn’t appear to offer much protection against infection by the Omicron variant.
The new study comes from a team led by Shan-Lu Liu at The Ohio State University, Columbus. They wanted to explore how well vaccine-acquired immune protection holds up over time, especially in light of newly arising SARS-CoV-2 variants.
This is an important issue going forward because mRNA vaccines train the immune system to produce antibodies against the spike proteins that crown the surface of the SARS-CoV-2 coronavirus. These new variants often have mutated, or slightly changed, spike proteins compared to the original one the immune system has been trained to detect, potentially dampening the immune response.
In the study, the team collected serum samples from 48 fully vaccinated health care workers at four key time points: 1) before vaccination, 2) three weeks after the first dose, 3) one month after the second dose, and 4) six months after the second dose.
They then tested the ability of antibodies in those samples to neutralize spike proteins as a correlate for how well a vaccine works to prevent infection. The spike proteins represented five major SARS-CoV-2 variants. The variants included D614G, which arose very soon after the coronavirus first was identified in Wuhan and quickly took over, as well as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529).
The researchers explored in the lab how neutralizing antibodies within those serum samples reacted to SARS-CoV-2 pseudoviruses representing each of the five variants. SARS-CoV-2 pseudoviruses are harmless viruses engineered, in this case, to bear coronavirus spike proteins on their surfaces. Because they don’t replicate, they are safe to study without specially designed biosafety facilities.
At any of the four time points, antibodies showed a minimal ability to neutralize the Omicron spike protein, which harbors about 30 mutations. These findings are consistent with an earlier study showing a significant decline in neutralizing antibodies against Omicron in people who’ve received the initial series of two shots, with improved neutralizing ability following an additional booster dose.
The neutralizing ability of antibodies against all other spike variants showed a dramatic decline from 1 to 6 months after the second dose. While there was a marked decline over time after both vaccines, samples from health care workers who’d received the Moderna vaccine showed about twice the neutralizing ability of those who’d received the Pfizer vaccine. The data also suggests greater immune protection in fully vaccinated healthcare workers who’d had a breakthrough infection with SARS-CoV-2.
In addition to recommending full vaccination for all eligible individuals, the Centers for Disease Control and Prevention (CDC) now recommends everyone 12 years and up should get a booster dose of either the Pfizer or Moderna vaccines at least five months after completing the primary series of two shots . Those who’ve received the Johnson & Johnson vaccine should get a booster at least two months after receiving the initial dose.
While plenty of questions about the durability of COVID-19 immunity over time remain, it’s clear that the rapid deployment of multiple vaccines over the course of this pandemic already has saved many lives and kept many more people out of the hospital. As the Omicron threat subsides and we start to look forward to better days ahead, it will remain critical for researchers and policymakers to continually evaluate and revise vaccination strategies and recommendations, to keep our defenses up as this virus continues to evolve.
 COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention. February 27, 2022.
 Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection. Evans JP, Zeng C, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Sci Transl Med. 2022 Feb 15:eabn8057.
 COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Feb 2, 2022.
COVID-19 Research (NIH)
Shan-Lu Liu (The Ohio State University, Columbus)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development
Posted on by Dr. Francis Collins
With Omicron now on so many people’s minds, public health officials and virologists around the world are laser focused on tracking the spread of this concerning SARS-CoV-2 variant and using every possible means to determine the effectiveness of our COVID-19 vaccines against it. Ultimately, the answer will depend on what happens in the real world. But it will also help to have a ready laboratory means for gauging how well a vaccine works, without having to wait many months for the results in the field.
With this latter idea in mind, I’m happy to share results of an NIH-funded effort to understand the immune responses associated with vaccine-acquired protection against SARS-CoV-2 . The findings, based on the analysis of blood samples from more than 1,000 people who received the Moderna mRNA vaccine, show that antibody levels do correlate, albeit somewhat imperfectly, with how well a vaccine works to prevent infection.
Such measures of immunity, known as “correlates of protection,” have potential to support the approval of new or updated vaccines more rapidly. They’re also useful to show how well a vaccine will work in groups that weren’t represented in a vaccine’s initial testing, such as children, pregnant women, and those with certain health conditions.
The latest study, published in the journal Science, comes from a team of researchers led by Peter Gilbert, Fred Hutchinson Cancer Research Center, Seattle; David Montefiori, Duke University, Durham, NC; and Adrian McDermott, NIH’s Vaccine Research Center, National Institute of Allergy and Infectious Diseases.
The team started with existing data from the Coronavirus Efficacy (COVE) trial. This phase 3 study, conducted in 30,000 U.S. adults, found the Moderna vaccine was safe and about 94 percent effective in protecting people from symptomatic infection with SARS-CoV-2 .
The researchers wanted to understand the underlying immune responses that afforded that impressive level of COVID-19 protection. They also sought to develop a means to measure those responses in the lab and quickly show how well a vaccine works.
To learn more, Gilbert’s team conducted tests on blood samples from COVE participants at the time of their second vaccine dose and again four weeks later. Two of the tests measured concentrations of binding antibodies (bAbs) that latch onto spike proteins that adorn the coronavirus surface. Two others measured the concentration of more broadly protective neutralizing antibodies (nAbs), which block SARS-CoV-2 from infecting human cells via ACE2 receptors found on their surfaces.
Each of the four tests showed antibody levels that were consistently higher in vaccine recipients who did not develop COVID-19 than in those who did. That is consistent with expectations. But these data also allowed the researchers to identify the specific antibody levels associated with various levels of protection from disease.
For those with the highest antibody levels, the vaccine offered an estimated 98 percent protection. Those with levels about 1,000 times lower still were well protected, but their vaccine efficacy was reduced to about 78 percent.
Based on any of the antibodies tested, the estimated COVID-19 risk was about 10 times lower for vaccine recipients with antibodies in the top 10 percent of values compared to those with antibodies that weren’t detectable. Overall, the findings suggest that tests for antibody levels can be applied to make predictions about an mRNA vaccine’s efficacy and may be used to guide modifications to the current vaccine regimen.
To understand the significance of this finding, consider that for a two-dose vaccine like Moderna or Pfizer, a trial using such correlates of protection might generate sufficient data in as little as two months . As a result, such a trial might show whether a vaccine was meeting its benchmarks in 3 to 5 months. By comparison, even a rapid clinical trial done the standard way would take at least seven months to complete. Importantly also, trials relying on such correlates of protection require many fewer participants.
Since all four tests performed equally well, the researchers say it’s conceivable that a single antibody assay might be sufficient to predict how effective a vaccine will be in a clinical trial. Of course, such trials would require subsequent real-world studies to verify that the predicted vaccine efficacy matches actual immune protection.
It should be noted that the Food and Drug Administration (FDA) would need to approve the use of such correlates of protection before their adoption in any vaccine trial. But, to date, the totality of evidence on neutralizing antibody responses as correlates of protection—for which this COVE trial data is a major contributor—is impressive.
Neutralizing antibody levels are also now being considered for use in future coronavirus vaccine trials. Indeed, for the EUA of Pfizer’s mRNA vaccine for 5-to-11-year-olds, the FDA accepted pre-specified success criteria based on neutralizing antibody responses in this age group being as good as those observed in 16- to 25-year-olds .
Antibody levels also have been taken into consideration for decisions about booster shots. However, it’s important to note that antibody levels are not precise enough to help in deciding whether or not any particular individual needs a COVID-19 booster. Those recommendations are based on how much time has passed since the original immunization.
Getting a booster is a really good idea heading into the holidays. The Delta variant remains very much the dominant strain in the U.S., and we need to slow its spread. Most experts think the vaccines and boosters will also provide some protection against the Omicron variant—though the evidence we need is still a week or two away. The Centers for Disease Control and Prevention (CDC) recommends a COVID-19 booster for everyone ages 18 and up at least six months after your second dose of mRNA vaccine or two months after receiving the single dose of the Johnson & Johnson vaccine . You may choose to get the same vaccine or a different one. And, there is a place near you that is offering the shot.
 Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.
Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O’Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA; Immune Assays Team§; Moderna, Inc. Team§; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team§; United States Government (USG)/CoVPN Biostatistics Team§. Science. 2021 Nov 23:eab3435.
 Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. N Engl J Med. 2021 Feb 4;384(5):403-416.
 A government-led effort to identify correlates of protection for COVID-19 vaccines. Koup RA, Donis RO, Gilbert PB, Li AW, Shah NA, Houchens CR. Nat Med. 2021 Sep;27(9):1493-1494.
 Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, Barnett ED, Muñoz FM, Maldonado Y, Pahud BA, Domachowske JB, Simões EAF, Sarwar UN, Kitchin N, Cunliffe L, Rojo P, Kuchar E, Rämet M, Munjal I, Perez JL, Frenck RW Jr, Lagkadinou E, Swanson KA, Ma H, Xu X, Koury K, Mather S, Belanger TJ, Cooper D, Türeci Ö, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591007 Clinical Trial Group. N Engl J Med. 2021 Nov 9:NEJMoa2116298.
 COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Nov 29, 2021.
COVID-19 Research (NIH)
Combat COVID (U.S. Department of Health and Human Services)
Peter Gilbert (Fred Hutchison Cancer Research Center)
David Montefiori (Duke University, Durham, NC)
Adrian McDermott (National Institute of Allergy and Infectious Diseases/NIH)
NIH Support: National Institute of Allergy and Infectious Diseases