Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial

Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously

“…We have previously reported the incidence of adverse reactions within 14 days post-boost, serious adverse events during the first 28 days post-boost vaccination, the serum NAbs against live SARS-CoV-2 virus and delta variants, receptor-binding domain (RBD)-specific binding IgG and IgA responses at days 14 and 28 after the booster dose, and SARS-CoV-2 spike-specific cytokine T cells responses after receiving a boost vaccination [11]. In this report, we revealed the neutralising antibodies (NAbs) against live wild-type SARS-CoV-2 and omicron variant and RBD-specific IgG antibodies in serum of the first 40 participants in each of the three treatment groups at months 3 and 6 after the booster dose.…”

“…We used the WHO International Standard (NIBSC code 20/136) as the reference for the cytopathic effect-based microneutralisation assays. We used the commercial Anti-SARS-CoV-2 RBD IgG ELISA kit (Vazyme Medical Technology, Nanjing, China) to measure RBD-specific IgG responses (RU/ml) with a cutoff titer of 1:10 [11].…”

“…The sample size calculation was based on the hypothesis that a booster vaccination with aerosolised Ad5-nCoV following the two doses of CoronaVac could elicit a non-inferior or superior serum NAbs response at 14 days after the booster dose compared with a third dose of CoronaVac does, which has been reported previously [11]. Serum NAbs titres against the wild-type SARS-CoV-2 virus and omicron (B.1.1.529) variant at day 28, month 3, and month 6 were measured in a subgroup of the first 40 participants out of 150 participants in each group.…”

“…In our previously reported study [11], a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV (by CanSino Biologics, China) induced substantial serum NAb titers against SARS-CoV-2, which were 6.7-10.7-fold stronger serum NAbs response than a homologous CoronaVac booster between days 14 and 28 after the booster dose. Participants who inhaled 0.1 mL and 0.2 mL of aerosolized Ad5-nCoV had NAb GMT peaks of 6054.1 and 4221.3 IU/mL against live SARS-CoV-2 virus, respectively, at day 28 after the booster vaccination, which was higher than three doses of BNT162b2 (955.7 IU/mL).…”

The Differentiation and Maintenance of SARS-CoV-2-Specific Follicular Helper T Cells

“…Notably, heterologous vaccination was used in the abovementioned infection/vaccination-booster stratagem, providing corroborative evidence to the effectiveness of the heterologous sequential vaccination strategy against mutant VOCs of SARS-CoV-2. Compared to homologous vaccination, multiple kinds of heterologous sequential immunization were proved to be superior to induce broad neutralization against VOCs, including combination of inactivated vaccine followed by heterologous mutant RBD vaccine ( Song et al., 2022 ), adenoviral vectored vaccine followed by mRNA vaccine ( Pozzetto et al., 2021 ), inactivated vaccine followed by mRNA vaccine ( Zuo et al., 2022 ), and inactivated vaccine followed by adenoviral vectored vaccine ( Li et al., 2022 ). Given the barely affected memory CD4 + T cell responses to peptide pool of Omicron S protein ( Naranbhai et al., 2022 ), it is thus clear that virus-specific memory T FH cells play an important role in the generation of potent and broad neutralizing antibodies to VOCs induced by the heterologous sequential vaccination strategy.…”