Heterologous booster with inhaled adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants

ABSTRACT

The rapid widespread Omicron subvariant BA.5 of SARS-CoV-2 has become a potential imminent pandemic threat, but available vaccines lack high efficacy against this subvariant. Thus, it is urgent to find highly protective vaccination strategies within available SARS-CoV-2 vaccines. Here, by using a SARS-CoV-2 pseudovirus neutralization assay, we demonstrated that the aerosol inhalation of adenoviral vector COVID-19 vaccine after two dose of inactivated vaccine (I-I-Ad5) led to higher levels of neutralizing antibodies against D614G strain (2041.00[95% CI, 1243.00–3351.00] vs 249.00[149.10–415.70]), Omicron BA.2 (467.10[231.00–944.40] vs 72.21[39.31–132.70]), BA.2.12.1(348.5[180.3–673.4] vs 53.17[31.29–90.37]), BA.2.13 (410.40[190.70–883.3] vs 48.48[27.87–84.32]), and BA.5 (442.40 vs 56.08[35.14–89.51]) than three inactivated vaccine doses (I-I-I). Additionally, the level of neutralizing antibodies against BA.5 induced by I-I-Ad5 was 2.41-fold higher than those boosted by a third dose of RBD subunit vaccine (I-I-S) (p = 0.1308). The conventional virus neutralizing assay confirmed that I-I-Ad5 induced higher titre of neutralizing antibodies than I-I-I (116.80[84.51–161.5] vs 4.40[4.00–4.83]). In addition, I-I-Ad5 induced higher, but later, anti-RBD IgG and IgA in plasma than I-I-I. Our study verified that mucosal immunization with aerosol inhalation of adenoviral vector COVID-19 vaccine may be an effective strategy to control the probable wave of BA.5 pandemic in addition to two inactivated vaccines.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• Omicron variant BA.5
• vaccination strategies
• adenovirus type 5 vector vaccine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [2019YFC0810900], Ministry of Science and Technology of the People Republic of China [2021YFC0864400], NSFC [81971485, 82271801], Guangdong Basic and Applied Basic Research Foundation [2019B1515120068, 2020B1111330001, 2022B1111070002], Emergency Key Program of Guangzhou Laboratory [No. EKPG21-30-1], China Postdoctoral Science Foundation [2021M690792] and Zhongnanshan Medical Foundation of Guangdong Province [ZNSA-2020013].