Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination

Abstract

Background The use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants. Methods A total of 224 individuals who completed the two-dose CoronaVac for six months were included. We studied reactogenicity and immunogenicity following a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the mRNA vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-months boosting intervals. Results The solicited adverse events (AEs) were mild to moderate and well-tolerated. Total RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T-cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222 and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups. Conclusions All four booster vaccines significantly increased binding and neutralizing antibody (NAbs) in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant.

Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

“…However, the NAb titers against omicron were retained upon booster vaccination even though the current vaccines composition was based on the ancestral strain. Consistent results were observed after receiving mRNA vaccine following either homologous inactivated, adenoviral-vectored, or mRNA-based vaccines prime [14,21,22,30]. Although the low number of omicron-neutralizing memory B-cells produced after two-doses of mRNA vaccination has previously been reported, their coverages were improved through affinity maturation over time and might be sufficient to expand the coverage of neutralization against SARS-CoV-2 variants after receiving a booster dose [31].…”

“…It was found that individuals who received the heterologous CoronaVac/AZD1222 vaccination exhibited a 5.9-fold reduction in binding antibody and less detectable NAbs to omicron variants after 4 to 5 months post-second dose, indicating waning of vaccine-induced immunity [10]. It has been well established that booster vaccinations could overcome the waning immunity [14,21,22,28]. Rapid elevation in binding antibodies after boosting with mRNA and adenoviral-vectored vaccines were found.…”

“…However, the vaccine effectiveness and capability of inducing immune responses differ with different types of vaccines and are affected by emerging variants [20]. Our previous study indicated that mRNA vaccine-or AZD1222-boosted individuals after a two-dose CoronaVac course elicited a higher immune response than in those receiving boosted inactivated vaccines [21]. In the COV-BOOST trial, the heterologous boost after either two-dose of AZD1222 or BNT162b2 prime showed an increased humoral and cell-mediated immune response compared 6 to homologous booster vaccination, although the reactogenicity was increasing in some heterologous boosted combination [22].…”

The Epidemiological, Clinical Features and Outcomes of Imported Chinese COVID-19 Patients Following Inactivated Vaccines Injection

“… 31 Booster vaccines are needed to increase neutralizing antibodies in fully vaccinated individuals. 18 , 19 …”

“… 17 , 18 However, different booster vaccines significantly increased neutralizing antibodies (NAbs) in patients with two doses of inactivated vaccines, including the omicron variant. 18 , 19 …”