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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals.

ABSTRACT: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2^1-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC₅₀s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

SUBMITTER: Robbiani DF

PROVIDER: S-EPMC7263513 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals.

Robbiani Davide F DF Gaebler Christian C Muecksch Frauke F Lorenzi Julio C C JCC Wang Zijun Z Cho Alice A Agudelo Marianna M Barnes Christopher O CO Gazumyan Anna A Finkin Shlomo S Hagglof Thomas T Oliveira Thiago Y TY Viant Charlotte C Hurley Arlene A Hoffmann Hans-Heinrich HH Millard Katrina G KG Kost Rhonda G RG Cipolla Melissa M Gordon Kristie K Bianchini Filippo F Chen Spencer T ST Ramos Victor V Patel Roshni R Dizon Juan J Shimeliovich Irina I Mendoza Pilar P Hartweger Harald H Nogueira Lilian L Pack Maggi M Horowitz Jill J Schmidt Fabian F Weisblum Yiska Y Michailidis Eleftherios E Ashbrook Alison W AW Waltari Eric E Pak John E JE Huey-Tubman Kathryn E KE Koranda Nicholas N Hoffman Pauline R PR West Anthony P AP Rice Charles M CM Hatziioannou Theodora T Bjorkman Pamela J PJ Bieniasz Paul D PD Caskey Marina M Nussenzweig Michel C MC

bioRxiv : the preprint server for biology 20200522

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2<sup>1-5</sup>. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days afte ...[more]

PMID: 32511384

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Project description:BackgroundUnderstanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches.MethodsWe evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test.FindingsIncreasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers.InterpretationHospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics.FundingAustin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.

Dataset Information

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals.

Publications

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals.

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