Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates

ABSTRACT

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

KEYWORDS:

• Heterologous prime-boost
• COVID-19 vaccine
• neutralizing antibody
• T cell response
• th1/th2 balance

Acknowledgments

This work was supported by the Major Special Projects Funding Program of the Ministry of Science and Technology of the People’s Republic of China under grant number 2020YFC0860500.

Disclosure statement

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

Author contributions

JW, MX, and ZL conceived the study. ZL, QH, and QM designed the study. QH, CA, JZ, and FG performed the experiments; QH, FG, and LB analyzed the data; QH, QM, and CL wrote the draft. All authors have reviewed and approved the final manuscript.

Data and materials availability

All data generated in this study are available from the corresponding author upon reasonable request. Pseudoviruses used for NAb measurements can be obtained from the Chinese National Institution for Food and Drug Control. The live SARS-CoV-2 used fo NAb measurements was isolated by Sinovac Research and Development Co., Ltd.

Ethics statement

All animal research protocols were approved by the Institutional Animal Care and Use Committee at National Institutes for Food and Drug Control, China (No. 2020-B015), and these protocols were conducted in accordance with regulations regarding the management of laboratory animals (National Science and Technology Commission no. 2 of Oct. 31, 1988) and “guidance notes on the treatment of experimental animals” (Chinese version (2006) no. 398). All institutional guidelines for animal care and use were strictly followed throughout the study.

Additional information

Funding

This work was supported by Major Special Projects Funding Program of the Ministry of Science and Technology of the People’s Republic of China. [grant number 2020YFC0860500].