Vaccines against SARS-CoV-2 variants and future pandemics

Abstract

Introduction: Vaccination continues to be the most effective method for controlling COVID-19 infectious diseases. Nonetheless, SARS-CoV-2 variants continue to evolve and emerge, resulting in significant public concerns worldwide, even after more than 2 years since the COVID-19 pandemic. It is important to better understand how different COVID-19 vaccine platforms work, why SARS-CoV-2 variants continue to emerge, and what options for improving COVID-19 vaccines can be considered to fight against SARS-CoV-2 variants and future pandemics.

Area covered: Here, we reviewed the innate immune sensors in the recognition of SARS-CoV-2 virus, innate and adaptive immunity including neutralizing antibodies by different COVID-19 vaccines. Efficacy comparison of the several COVID-19 vaccine platforms approved for use in humans, concerns about SARS-CoV-2 variants and breakthrough infections, and the options for developing future COIVD-19 vaccines were also covered.

Expert opinion: Owing to the continuous emergence of novel pathogens and the reemergence of variants, safer and more effective new vaccines are needed. This review also aims to provide the knowledge basis for the development of next-generation COVID-19 and pan-coronavirus vaccines to provide cross-protection against new SARS-CoV-2 variants and future coronavirus pandemics.

Keywords: SARS-CoV-2: ACE-2; TMPRSS-2; nucleic-acid-based vaccine; universal vaccine.

Figure 1.

Domain arrangement of the SARS-CoV-2 S glycoprotein. S1 comprises a signal sequence, NTD, and RBD. S2 comprises FP, HR1, HR2, the TM domain, and cytoplasmic C-terminus. NTD, N-terminal domain; RBD, receptor-binding domain; FP, fusion peptide; IFP, internal fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; TM, transmembrane domain. The spike protein sequences of the SARS-CoV-2 variants were aligned using MAGAX webserver.

Figure 2.

The differences in airway tissue expression of ACE2 and TMPRSS2 between healthy and compromised elderly population. SARS-CoV-2 infection leads to an imbalance in vascular homeostasis by hijacking ACE2 in the elderly population and patients with comorbid diseases. Compared to ACE2 and TMPRSS2 expression levels in the elderly population, healthy people with low expression of this receptor and protease have a higher infection transmission capacity without the severe pathogenesis of SARS-CoV-2. After SARS-CoV-2 infection, more inflammatory immune cells such as neutrophils, monocytes migrate to the alveoli and enhance lung inflammation and pathogenesis, increasing vascular permeability, ultimately leading to edema. This figure was created using the BioRender web-based software.

Figure 3.

Fates of DNA, RNA, and protein-based vaccines. After the DNA vaccine is taken up by antigen-presenting cells (APCs), the DNA should undergo a two step-journey of transcription and translation to express the encoded protein. After un-coating of the nano-system, the released mRNA undergoes translation to express the encoded protein through a cytosolic antigen process. Vaccine antigen can be presented to naive T cells through the major histocompatibility complex (MHC) pathways. CD8 + T cell is predominantly activated by endogenously expressed antigens presented on MHC class I molecules. CD4 + T helper cell activation is triggered through MHC class II from APC. In humoral immune response, B cells cognate vaccine antigens and retrieve CD4 + T cells for the differentiation into antibody secreting plasma cells. The protein-based SARS-CoV-2 vaccine directly and specifically targets B cells via B cell-receptors and APCs. This figure was created using the BioRender web-based software.

Figure 4.

Universal SARS-CoV-2 vaccine approaches. (A) Spike protein is a major immunogen to induce neutralizing antibodies and, with a certain degree, T cell immunity. (B) Matrix and envelope proteins have a relatively conserved sequence and are targets for cross reactive T cell response against different variants. (C) Abundant nuclear proteins are a target for cellular immunity during SARS-CoV-2 infection. (D) Non-structural protein (Nsp) has a relatively conserved sequence among the SARS-CoV-2 variants. T cell epitopes can induce cross reactive and broad immunity against variants. This figure was created using the BioRender web-based software.