Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 77), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68–100 days). Blood samples were collected at a median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants, including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2), were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which exceeds 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant.

Highlights

  • Since the commencement of the coronavirus disease 2019 (COVID-19) outbreak at the end of 2019, there have been more than 313 million cases of infection [1]

  • This study aims to determine antibody levels and cross-neutralization in patients with SARS-CoV-2 breakthrough infection, following two doses of CoronaVac, compared with those in uninfected individuals who received two doses of CoronaVac, and those who received AZD1222 as a third vaccination

  • Patients who had been completely vaccinated with two doses of CoronaVac subsequently became infected with SARS-CoV-2 as determined via a positive polymerase chain reaction (PCR) test were recruited at the Center of Excellence in Clinical Virology between 21 April and 20 September 2021

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Summary

Introduction

Since the commencement of the coronavirus disease 2019 (COVID-19) outbreak at the end of 2019, there have been more than 313 million cases of infection [1]. In Thailand, the CoronaVac vaccine was approved for Thai adults, aged 18–59, and a mass vaccination campaign was started in late February 2021 [2]. The AZD1222 was approved in the following month for adults ≥18 years, this vaccine was prioritized for the elderly, ≥60 years of age, and individuals who had underlying diseases due to a shortage in vaccine supply. AZD1222 is Chimpanzee adenovirus Oxford 1 (ChAdOx1)-vectored vaccine, containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein [4]. Reduced viral susceptibility to vaccine-induced antibodies due to the emergence of SARS-CoV-2 variants, together with the waning of vaccine-induced immunity, is increasing the incidence of COVID-19 breakthrough infection after vaccination [5,6]. Several studies indicated that the neutralizing antibody titres against omicron increase after boosting with the third dose of viral vectored vaccine or mRNA vaccine [8–11]. The study of immunogenicity and neutralization of SARS-CoV-2 variants, omicron (B.1.1.529), is limited [8]

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