A comparative analysis of vaccine immunity induced by heterologous booster with Ad5-nCoV via different routes of administration

MA Wenxuan; HAN Yuhong; LIN Ang; ZHAO Weijun

doi:10.11665/j.issn.1000-5048.2024011701

Journal of China Pharmaceutical University > 2024 > 55(1): 137-146. > DOI: 10.11665/j.issn.1000-5048.2024011701

MA Wenxuan, HAN Yuhong, LIN Ang, et al. A comparative analysis of vaccine immunity induced by heterologous booster with Ad5-nCoV via different routes of administration[J]. J China Pharm Univ, 2024, 55(1): 137 − 146. DOI: 10.11665/j.issn.1000-5048.2024011701

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A comparative analysis of vaccine immunity induced by heterologous booster with Ad5-nCoV via different routes of administration

MA Wenxuan¹,
HAN Yuhong²,
LIN Ang^1, ,,
ZHAO Weijun^{2, 3, ,}

1.
Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198
2.
Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198
3.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 32200764) and the Natural Science Foundation of Jiangsu Province (No. BK20221031)

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Received Date: January 16, 2024
Available Online: March 05, 2024

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Abstract

Abstract

Heterologous boost COVID-19 vaccination can solved the problem of decreased efficacy caused by single dose of vaccine. Heterologous booster with adenoviral-vectored COVID-19 vaccine (Ad5-nCoV) following primary immunization with inactivated COVID-19 vaccines is a widely-used vaccination strategy in clinic, while different routes of Ad5-nCoV administration exist and pose a question which route could be more optimal. In this study, we comprehensively evaluated and compared the vaccine immunity induced in mice immunized according to three different vaccination regimens: “3×phosphate buffered solution(3× PBS)”, “2×inactivated vaccine + 1×inactivated vaccine (3×INA)”, “2×inactivated vaccine + 1×Ad5-nCoV (intramuscular)[2×INA+Ad5(im)]”and“2×inactivated vaccine + 1×Ad5-nCoV (intranasal)[2×INA+Ad5(in)]”. We found that heterologous booster with Ad5-nCoV, irrespective of the route of administration, induced significantly higher levels of anti-Spike IgG and subclasses (IgG1and IgG2c), Spike-specific T cells, class-switched Spike⁺ memory B cells (MBCs) than homologous booster with 3^rd dose of inactivated COVID-19 vaccine. Of note, compared with the intramuscular given, intranasal given of Ad5-nCoV as a booster dose clearly induced higher levels of serum and bronchoalveolar bavage fluid anti-spike immunoglobulin A, and moreover, induced stronger infiltration of major innate effector cells like neutrophils, natural killer cells and dendritic cells into the lung tissue, which suggested that mucosal vaccine responses are generated upon intranasal booster with Ad5-nCoV. Altogether, our study analyzed the vaccine immunity induced by different COVID-19 vaccines administered using different regimens, which may guide the clinical use of other types of prophylactic vaccines aiming to mount improved vaccine responses.
- COVID-19 vaccines,
- heterologous booster,
- homologous booster,
- route of administration,
- immunogenicity,
- mucosal response

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