Johnson & Johnson vaccine
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
Posted on by Dr. Francis Collins
There are many reasons to be excited about the three COVID-19 vaccines that are now getting into arms across the United States. At the top of the list is their extremely high level of safety and protection against SARS-CoV-2, the coronavirus that causes COVID-19. Of course, those data come from clinical trials that were rigorously conducted under optimal research conditions. One might wonder how well those impressive clinical trial results will translate to the real world.
A new study published in the New England Journal of Medicine  offers an early answer for the Pfizer/BioNTech vaccine. The Pfizer product is an mRNA vaccine that was found in a large clinical trial to be up to 95 percent effective in preventing COVID-19, leading to its Emergency Use Authorization last December.
The new data, which come from Israel, are really encouraging. Based on a detailed analysis of nearly 600,000 people vaccinated in that nation, a research team led by Ran Balicer, The Clalit Research Institute, Tel Aviv, found that the risk of symptomatic COVID-19 infection dropped by 94 percent a week after individuals had received both doses of the Pfizer vaccine. That’s essentially the same very high level of protection that was seen in the data gathered in the earlier U.S. clinical trial.
The study also found that just a single shot of the two-dose vaccine led to a 57 percent drop in the incidence of symptomatic COVID-19 infections and a 62 percent decline in the risk of severe illness after two to three weeks. Note, however, that the protection clearly got better after folks received the second dose. While it’s too soon to say how many lives were saved in Israel thanks to full vaccination, the early data not surprisingly suggest a substantial reduction in mortality.
Israel, which is about as large as New Jersey with a population of around 9 million, currently has the world’s highest COVID-19 vaccination rate. In addition to its relatively small size, Israel also has a national health system and one of the world’s largest integrated health record databases, making it a natural choice to see how well one of the new vaccines was working in the real world.
The study took place from December 20, 2020, the start of Israel’s first vaccination drive, through February 1, 2021. This also coincided with Israel’s third and largest wave of COVID-19 infections and illness. During this same period, the B.1.1.7 variant, which was first detected in the United Kingdom, gradually became Israel’s dominant strain. That’s notable because the U.K. variant spreads from person-to-person more readily and may be associated with an increased risk of death compared with other variants .
Balicer and his colleagues reviewed data on 596,618 fully vaccinated individuals, ages 16 and older. A little less than one third—about 170,000—of the people studied were over age 60. To see how well the vaccine worked, the researchers carefully matched each of the vaccinated individuals in the study to an unvaccinated person with similar demographics as well as risks of infection, severe illness, and other important health attributes.
The results showed that the vaccine works remarkably well. In fact, the researchers determined that the Pfizer/BioNTech vaccine is similarly effective—94 percent to 96 percent—across adults in different age groups. It also appears that the vaccine works about equally well for individuals age 70 and older as it does for younger people.
So far, more than 92 million total vaccine doses have been administered in the U.S. With the Janssen COVID-19 vaccine (also called the Johnson & Johnson vaccine) now coming online, that number will rise even faster. For those of you who haven’t had the opportunity just yet, these latest findings should come as added encouragement to roll up your sleeve for any one of the authorized vaccines as soon as your invitation arrives.
 BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernán MA, Lipsitch M, Reis B, Balicer RD. N Engl J Med. 2021 Feb 24.
 Emerging SARS-CoV-2 Variants. Centers for Disease Control and Prevention.
COVID-19 Research (NIH)
Clalit Research Institute (Tel Aviv, Israel)
Ran Balicer (Clalit Research Institute)