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

Jiaying Zhong; Shuo Liu; Tingting Cui; Jingxin Li; Fengcai Zhu; Nanshan Zhong; Weijin Huang; Zhuxiang Zhao; Zhongfang Wang

doi:10.1080/22221751.2022.2132881

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

Emerg Microbes Infect. 2022 Dec;11(1):2689-2697. doi: 10.1080/22221751.2022.2132881.

Authors

Jiaying Zhong^{1

2}, Shuo Liu³, Tingting Cui^{1

2}, Jingxin Li⁴, Fengcai Zhu⁴, Nanshan Zhong^{1

2}, Weijin Huang³, Zhuxiang Zhao⁵, Zhongfang Wang^{1

2}

Affiliations

¹ State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China.
² Guangzhou Laboratory, Guangzhou, People's Republic of China.
³ National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products & NMPA Key Laboratory for Quality Research and Evaluation of Biological Products Beijing, Beijing, People's Republic of China.
⁴ NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China.
⁵ Department of Infectious Disease, Respiratory and Critical Care Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.

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; Omicron variant BA.5; SARS-CoV-2; adenovirus type 5 vector vaccine; vaccination strategies.

MeSH terms

Adenoviridae / genetics
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
SARS-CoV-2
Vaccines, Inactivated
Viral Vaccines*

Substances

COVID-19 Vaccines
Antibodies, Neutralizing
Viral Vaccines
Antibodies, Viral
Vaccines, Inactivated

Supplementary concepts

SARS-CoV-2 variants

Grants and 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].