Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection.
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ABSTRACT:
SUBMITTER: Bates TA
PROVIDER: S-EPMC8678894 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection.
Bates Timothy A TA McBride Savannah K SK Winders Bradie B Schoen Devin D Trautmann Lydie L Curlin Marcel E ME Tafesse Fikadu G FG
JAMA 20220101 2
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Project description:Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.
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Project description:BackgroundThe role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected.ObjectivesThe goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses.MethodsSerum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit.ResultsAt baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels.ConclusionsOur data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.
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Project description:BackgroundThe immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories.MethodsThe neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination.FindingsOmicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies.ConclusionsImmune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants.FundingThis study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
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