ABSTRACT
Background Booster vaccination is important because of waning immunity and variant immune evasion. We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. Methods and findings HCW at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2, half-dose mRNA-1273, mRNA-1273, and MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. 340 HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. Anti-spike IgG increased by a fold of 8.4 for MCV-COV1901, 32.2 for BNT162b2, 47.6 for half-dose mRNA-1273 and 63.2 for mRNA1273. The live virus microneutralization assay (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron variant were 6.4 to 13.5 times lower than those against the wild type. Serum neutralizing antibody against omicron variant was undetectable in 60% of the participants who received MCV-COV1901 as a booster by LVMNA. By using pseudovirus neutralizing assay, we found that neutralization activity in the four groups against omicron variant were 4.6 to 5.2 times lower than that against the D614G. All booster vaccines induced comparable T cell response. Conclusions Third dose booster not only increases neutralizing antibody titer but also enhances antibody capacity against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those after primary series of ChAdOx1 nCov-19.
ABSTRACT
Background: Four members in the Coronaviruses family including 229E circulating in the community were known to cause mild respiratory tract infections in humans. The epidemiologic information of the seasonal human coronavirus (HCoV) may help gain insight into the development of the ongoing pandemic of coronavirus disease since 2019 (COVID-19). Methods Plasma collection containing 1558 samples was obtained in 2010 for an estimate of the prevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan. Of 1558 samples, 200 were randomly selected from those aged < 1 year to > 60 years. The neutralizing antibody titers to HCoV-229E were determined in the serums using live virus ATCC VR_740TM cultivating in the Huh_ 7 cell line. Results Seroconversion of HCoV-229E (titer ≥ 1:2) was identified as early as less than 5 years of age. Among 140 subjects aged younger than or equal to 40 years, all of them had uniformly low titers (< 1:10) and the geometric mean titers (GMTs) were not significantly different for those aged 0-5, 6-12, 13-18 and 19-40 years (P > 0.1). For 60 subjects greater than 40 years old, a majority (39, 65%) of them had high titers ≥ 1:10 and the GMTs were significantly increased with advanced age (P < 0.0001). Age was the most significant factor predicting seropositivity in the multivariate analysis, with an adjusted odds ratio of 1.107 and a 95% adjusted confidence interval of 1.061-1.155 (P < 0.0001). Conclusion HCoV-229E infection occurred as early as younger than 5 years old in Taiwanese and the magnitudes of neutralizing titers against HCoV-229E increased with advanced age beyond 40 years.