Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

Khoury, David S.; Cromer, Deborah; Reynaldi, Arnold; Schlub, Timothy E.; Wheatley, Adam K.; Juno, Jennifer A; Subbarao, Kanta; Kent, Stephen J.; Triccas, James A.; Davenport, Miles P.

doi:10.1038/s41591-021-01377-8

Cited by 3,469 publications

(3,886 citation statements)

References 59 publications

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“…Overall, our data also suggest that serum-based neutralization studies may provide a good proxy for real-life protection in the case of SARS-CoV-2 (ref. 18 ). Although this remains to be tested in a more widespread manner, it suggests that neutralization studies may be valid as a prompt first step before the establishment of real-world studies in the case of the emergence of new SARS-CoV-2 VOCs.…”

Section: Discussionmentioning

confidence: 99%

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Kustin

Harel

Finkel

et al. 2021

Nat Med

304

178

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The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.

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Section: Discussionmentioning

confidence: 99%

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Kustin

Harel

Finkel

et al. 2021

Nat Med

304

178

View full text Add to dashboard Cite

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“…Importantly, Fc effector functions were readily detectable above uninfected controls in 94% of subjects for all assays at the last time point sampled, in contrast with neutralization activity, which remained detectable above background for only 70% of subjects. Although neutralizing antibodies are likely to form a correlate of protection for SARS-CoV-2, 7,32 several studies find that neutralizing antibodies in convalescent donors with mild COVID-19 wane rapidly. 2,8,9 The rapid decline of plasma neutralization activity in the early weeks following infection is likely in part explained by the rapid decline of plasma IgM and IgA titers against S and RBD, 20,33 which substantially contribute to neutralization of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Lee

Selva

Davis

et al. 2021

Cell Reports Medicine

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The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We develop assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19, up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last timepoint studied (94%) in contrast with neutralisation activity (70%). While it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralising antibodies.

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“…Relative antibody levels were also compared to the median levels of convalescent serum taken 21-115 days post symptom onset in patients with COVID 19; expression of vaccination-induced antibody levels to convalescent individuals helps to define correlates of protection. 10 The association between reactogenicity following second vaccine dose and the proportion of patients with anti-spike or anti-RBD seroconversion two weeks following second dose was assessed by a Chi-Squared test.…”

Section: Study Design and Methodsmentioning

confidence: 99%

The Humoral Response to the BNT162b2 Vaccine in Hemodialysis Patients

Yau

Abe

Naimark

et al. 2021

Preprint

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Importance: Hemodialysis patients have an exceptionally high mortality from COVID-19 and this patient population often has a poor response to vaccinations. Randomized controlled trials for COVID-19 vaccines included few patients with kidney disease, therefore vaccine immunogenicity is uncertain in this population. Objective: Evaluate the SARS-CoV-2 antibody response in chronic hemodialysis patients following one versus two doses of BNT162b2 COVID-19 vaccination compared to health care worker controls and convalescent serum. Design: Prospective observational cohort study. Setting: Single centre study in Toronto, Ontario, Canada. Participants: 142 in-centre hemodialysis patients and 35 health care worker controls. Exposure: BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Main Outcomes and Measures: SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP) were measured in 66 hemodialysis patients receiving one vaccine dose following a public health policy change, 76 patients receiving two vaccine doses, and 35 health care workers receiving two vaccine doses. Results: Detectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15/142 (11%) of patients at baseline while only three patients had prior RT-PCR confirmed COVID-19. Two additional patients contracted COVID-19 after receiving two doses of vaccine. In patients receiving a single BNT162b2 dose, seroconversion occurred in 53/66 (80%) for anti-spike and 35/66 (55%) for anti-RBD by 28 days post dose, but only 15/66 (23%) and 4/66 (6%), respectively attained a robust response as defined by reaching the median level of anti-spike and anti-RBD in convalescent serum from COVID-19 survivors. In patients receiving two doses of BNT162b2 vaccine, seroconversion occurred in 69/72 (96%) for anti-spike and 63/72 (88%) for anti-RBD by 2 weeks following the second dose while 52/72 (72%) and 43/76 (41%) reached the median convalescent serum level of anti-spike and anti-RBD, respectively. In contrast, 35/35 (100%) of health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2-4 weeks after the second dose. Conclusions and Relevance: This study confirms poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules, and avoiding delay of the second dose in these at-risk individuals.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

Cited by 3,469 publications

References 59 publications

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

The Humoral Response to the BNT162b2 Vaccine in Hemodialysis Patients

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