A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens

Author:

Zhang Panli12,Luo Shengxue3,Zou Peng12,Deng Qitao12,Wang Cong12,Li Jinfeng4,Cai Peiqiao5,Zhang Ling1,Li Chengyao1ORCID,Li Tingting1ORCID

Affiliation:

1. Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, China

2. Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company , Guangzhou , China

3. Department of Pediatrics, Shenzhen Hospital, Southern Medical University , Shenzhen, China

4. Shenzhen Bao'an District Central Blood Station , Shenzhen, China

5. Department of Bioengineering, School of Medicine and College of Engineering, University of Washington , Seattle, Washington, USA

Abstract

ABSTRACT The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in the respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus-vectored COVID-19 vaccine (Sad23L-nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1 × 10 9 PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S-BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T-cell response in lung compared with IM route, but lower T-cell response in spleen. By prime-boost vaccination regimens with different combinations of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN-involved vaccination stimulated higher protective mucosal or local immunity in BAL and lung, while the IM-involved immunization induced higher systemic immunity in serum and spleen. A long-term sustained mucosal and systemic NAb and T- cell immunity to SARS-CoV-2 was maintained at high level over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induce effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection. IMPORTANCE The essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including vaccine vector, delivery route, and boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimens by constructing a novel simian adenovirus-vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention.

Funder

MOST | National Natural Science Foundation of China

GDSTC | Natural Science Foundation of Guangdong Province

GDSTC | Basic and Applied Basic Research Foundation of Guangdong Province

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

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