SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination

Pajón, Rolando; Doria‐Rose, Nicole A.; Shen, Xiaoying; Schmidt, Stephen D.; O’Dell, Sijy; McDanal, Charlene; Feng, Wenhong; Jin, Tao; Eaton, Amanda; Maglinao, Maha; Tang, Haili; Manning, Kelly; Edara, Venkata-Viswanadh; Lai, Lilin; Ellis, Madison; Moore, Kathryn M.; Floyd, Katharine; Foster, Stephanie L.; Posavad, Christine M.; Atmar, Robert L.; Lyke, Kirsten E.; Zhou, Tongqing; Wang, Lingshu; Zhang, Yi; Gaudinski, Martin R.; Black, Walker P; Gordon, Ingelise J.; Guech, Mercy; Ledgerwood, Julie E.; Misasi, John; Widge, Alicia T.; Sullivan, Nancy J.; Roberts, Paul C.; Beigel, John H.; Korber, Bette; Baden, Lindsey R.; Sahly, Hana M. El; Chalkias, Spyros; Zhou, Honghong; Feng, Jing; Girard, Bethany; Das, Rituparna; Aunins, Anne; Edwards, Darin K.; Suthar, Mehul S.; Mascola, John R.; Montefiori, David C.

doi:10.1056/nejmc2119912

Cited by 378 publications

(376 citation statements)

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“…Plasma neutralizing antibodies elicited by mRNA vaccination are more potent against Wuhan-Hu-1 than variants 9,10 . Consistent with prior reports 3,7,[11][12][13] , the 3 rd vaccine dose significantly boosts geometric mean NT50s 16-fold, 12-fold and 37-fold for the Beta, Delta and Omicron variant, respectively.…”

Section: Plasma Binding and Neutralizationsupporting

confidence: 88%

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose

Muecksch

Wang

Cho

et al. 2022

Preprint

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The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals. The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain. The 3rd mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection. Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses. We find that the 3rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2nd vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2nd vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3rd dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

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Section: Plasma Binding and Neutralizationsupporting

confidence: 88%

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose

Muecksch

Wang

Cho

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…In addition, there is evidence that protection against disease gradually declines as the serum antibody level decreases [ 28 , 29 , 30 ]. Importantly though, the humoral immune response against the omicron variant can be restored by administration of booster doses [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Vaccination and Rates of Infections, Hospitalizations, ICU Admissions, and Deaths in the European Economic Area during Autumn 2021 Wave of SARS-CoV-2

Sikora

Rzymski

2022

Vaccines

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The COVID-19 vaccination campaigns were met with a varying level of vaccine hesitancy in Europe. We analyzed the potential relationships between COVID-19 vaccine coverage in different countries of the European Economic Area and rates of infection, hospitalizations, admissions to intensive care units (ICU), and deaths during the autumn 2021 SARS-CoV-2 wave (September−December). Significant negative correlations between infection rates and the percentage of fully vaccinated individuals were found during September, October, and November, but not December. The loss of this protective effect in December is likely due to the emergence of the omicron (B.1.1.529) variant, better adapted to evade vaccine-induced humoral immunity. For every considered month, the negative linear associations between the vaccine coverage and mean number of hospitalizations (r= −0.61 to −0.88), the mean number of ICU admissions (r= −0.62 to −0.81), and death rate (r= −0.64 to −0.84) were observed. The results highlight that vaccines provided significant benefits during autumn 2021. The vaccination of unvaccinated individuals should remain the primary strategy to decrease the hospital overloads, severe consequences of COVID-19, and deaths.

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“…Durability of the immune response against Omicron, especially after the booster dose, is an important consideration when deciding if and when an additional booster is needed. A recent analysis of the durability of antibody responses following mRNA-1273 primary and booster immunizations 13 revealed that neutralizing antibodies against the prototype D614G variant -which was dominant at the time when the Moderna and Pfizer vaccines showed outstanding efficacy that led to their Emergency Use Authorizations -declined 7.8-fold from 1 month to 7 months after the second mRNA immunization, whereas the decline from 1 month to 6 months after the booster was only 2.3-fold. This suggests improved durability after the boost; however, the response against Omicron declined 6.3-fold over the same 6-month time frame after the boost.…”

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confidence: 99%