A systematic review of SARS-CoV-2 vaccine candidates

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.

Fig. 1

The immune responses induced by SARS-CoV-2. a Innate immune response. SARS-CoV-2 infection induces imbalanced host immune responses, such as low IFN-I and -III levels but high pro-inflammatory cytokines. Nsp13 of SARS-CoV-2 targets the IFN pathway by associating with TBK1. The ORF6 protein interacts with the mRNA export factor NUP98-Rae1. The ORF9b indirectly interacts with MAVS via its interaction with Tom70. b Adaptive immune response. CD4⁺ T-cell responses are primarily directed against the S, M, and N proteins and partially against nsp3, nsp4, and ORF8. CD8⁺ T cells recognize SARS-CoV-2 M, N, S proteins, nsp6, and ORF3a. ORF8 is able to downregulate MHC-I expression on diverse cell types. SARS-CoV-2 primarily induces S protein- and RBD-specific IgG, while IgM and IgA responses are lower

Fig. 2

Overview of the diverse types of vaccines, and their potential advantages and disadvantages

Fig. 3

NAbs against CoVs and the scheme of Reverse Vaccinology 2.0. a NAbs, such as mAbs, single-domain antibodies, scFvs, and Fabs, are able to target viral proteins, with RBD being the most potent target. This process may further block receptor binding and membrane fusion, commonly via targeting the S1 and/or S2 subunit. b The scheme of Reverse Vaccinology 2.0. Antibodies are isolated from convalescent patients and tested for their efficacy in vitro and in vivo. NAbs are further studied in complex with the antigen. Identifying the epitopes may aid in immunogen design, which will later be evaluated in animal models and humans

Fig. 4

NAbs isolation strategies. a mAbs can be isolated from convalescent people previously infected with virus. After sorting antigen-specific B cells, deep sequencing can help pair the heavy- and light-chain genes. Selected pairs via functional screening can be used to produce mAbs. b Humanized mAbs can be isolated from immunized transgenic animal models, like mice. c Nanobodies can be constructed based on sequences of the camelid immunized with viral proteins and produced by phage carrying the VHH encoding sequences

Fig. 5

The immune responses induced by vaccines. Antigen-presenting cells (APCs) can process vaccine antigen and present it to CD8⁺ T cells and CD4⁺ T cells. CD8⁺ T cells can be stimulated by Th1 cytokines and in turn acquires the ability to attack the infected cells. Th2 cytokines can aid in the differentiation of B cells. The activated B cells can produce NAbs. However, imbalanced immune responses have the potential to cause pulmonary immunopathology, partially due to aberrant Th2 response or ADE

Fig. 6

Potential strategies to optimize vaccines. a DNA vaccines linked with calreticulum or the cDNA of human β₂-microglobulin and the α-1 and α-2 domains of MHC-I heavy chain can facilitate antigen presentation and induce the CTL response more directly. b Adjuvants have the potential to promote the immune response against CoVs, although several are involved in the immunopathology. c Certain types of vaccines can be delivered into host cells via gene gun, electropolaration, or LNP, thereby resulting in a broader protective immunity. d DNA vaccines linked with recombinant protein targeting the DC molecules, DEC-205, can induce potent humoral and cellular immune responses