Int J Biol Sci 2022; 18(12):4629-4641. doi:10.7150/ijbs.73583 This issue


Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review

Zhonghao Chen*, Ying Zhang*, Meng Wang*, Md Sahidul Islam, Ping Liao, Yuanjia Hu, Xin Chen

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
*These authors have contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Chen Z, Zhang Y, Wang M, Islam MS, Liao P, Hu Y, Chen X. Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review. Int J Biol Sci 2022; 18(12):4629-4641. doi:10.7150/ijbs.73583. Available from

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Graphic abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2- or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus.

Keywords: SARS-COV-2, Omicron variant, vaccine, booster dose, humoral immune response, cellular immune response