Frontiers in the COVID-19 vaccines development

Abstract

Novel corona virus caused pneumonia first reported in December, 2019 in Wuhan, China was later named COVID-19. Due to its special pathogenicity, COVID-19 transmitted with high speed beyond borders and has significantly affected normal life. Currently, no specific drugs, treatment or vaccines are available. Vaccine development for COVID-19 is a highly complex process involving viral genomic studies, identification of target for vaccine, vaccine design, manufacturing, storage and distribution, preclinical and clinical safety and efficacy studies. The high levels of efforts and global collaboration at this scale is unprecedented. The World Health Organization (WHO) has documented 160 different COVID-19 vaccine candidates as of July 13, 2020 with 26 currently on clinical evaluation while 137 vaccines on preclinical evaluation. COVID-19 vaccine efforts mark the first use of mRNA-type vaccines ever evaluated. Numerous research organizations have successfully initiated clinical evaluation of COVID-19 vaccines. This review aims to summarize the advances and challenges for COVID-19 vaccines development.

To the editor,

On December 31, 2019, novel corona virus caused pneumonia was first reported in Wuhan, China. The pathogen was soon identified as a novel corona virus from unknown origin and then was named as “corona virus of 2019” or “COVID-19”. With a rapid spread of the virus, WHO declared a global pandemic on March 11, 2020. According to WHO, as of July 14, 2020, almost all countries in the world have been affected with 12,768,307 confirmed cases and 566,654 confirmed deaths due to COVID-19 (https://covid19.who.int/). Its highly infectious and asymptomatic transmission characteristics have made it to a pandemic in a short time [1]. Vaccines are an essential countermeasure urgently needed to control the pandemic.

2-dimension and 3-dimension studies demonstrated COVID-19 virus as RNA stranded virus, surrounded by membrane (M) protein, envelope (E) protein, and the spike (S) structural protein. Genome of virus is highly packed inside nucleocapsid (N) protein which is enveloped by M, E and S protein [2]. Five nonstructural proteins including ORF1ab, ORF3a, ORF7, ORF8, ORF9 and ORF10 play a critical rule in adhesion of virus to host cell and can compromise vaccine efficacy [3]. SARS-CoV-2 shares genetic homology with other coronaviruses found in bats and its closest related human virus, SARS-CoV-1. The spike protein of SARS-CoV-2 has high identity with that of SARS and MERS, which might indicate the similarity of immune evasion mechanism. After publication of the full RNA genetic sequence of COVID-19 from infected patients by Chinese researchers on January 10, 2020 [2], many organizations around the world started to develop vaccines, based on knowledge obtained from SARS and MERS vaccine development, by different means including inactivated whole COVID-19 virus [4,5,6], live attenuated virus, adenovirus-based recombinant vector RNA and DNA vaccines [Fig. 1]. As of August 24, 2020, WHO documented a total of 160 vaccine candidates against COVID-19, with 26 vaccines currently in clinical evaluation (Table 1) and 137 under pre-clinical evaluation [7]. In order to get herd immunity, an estimated 67% of population needs to be vaccinated to stop the virus spreading [8]. A vaccine targeting the Spike protein receptor-binding domain (S-RBD) of SARS-CoV-2 induces protective immunity [9] in phase II/III human evaluation, after safety and efficacy results in rhesus macaque [10]. Meanwhile, the Ad5 vectored COVID-19 vaccine targeting the spike glycoprotein showed tolerability and immunogenicity at 28 days post-vaccination (NCT04313127) [11]. A few recent studies demonstrated promising results. The Ad5-vectored COVID-19 vaccine at 5 × 10¹⁰ viral particles was safe, and induced significant immune responses in the majority of recipients after a single immunization (NCT04341389) [12]. Analysis of 2 randomized phase 1 and phase 2 clinical trials of inactivated vaccine showed that patients had a low rate of adverse reactions and demonstrated immunogenicity (ChiCTR2000031809) [13]. Phase 1/2 single-blind, randomised controlled trial with adenovirus vaccine that expresses the spike protein of SARS-CoV-2 in chimpanzee (ChAdOx1 nCoV-19) showed an acceptable safety profile, and homologous boosting increased antibody responses [14]. Meanwhile clinical trial of mRNA-1273 vaccine results showed vaccination of nonhuman primates induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung [15, 16]. Another mRNA-based vaccine BNT162 was initiated phase I/II trial in China (ChiCTR2000034825).

Fig. 1

Data modified from the WHO website: https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf

Distribution of COVID-19 vaccine types under development.

Table 1 26 candidate vaccines in clinical evaluation

Both live-attenuated vaccines and inactivated vaccines are highly established in product development and manufacturing process but require handling live virus. Meanwhile recombinant protein-based and vector-based vaccines are safe but require epitope selection, antigen design, and vehicle development. Some new-generation vaccine types were not produced on large scale before. RNA and DNA vaccines are two new vaccine technologies currently in focus for COVID-19 vaccine development.

Vaccine development for COVID-19 is a highly complex process involving viral genomic studies, identification of target for vaccine, vaccine design, manufacturing, storage and distribution, preclinical and clinical safety and efficacy studies. The high levels of efforts and global collaboration at this scale is unprecedented. Due to the special nature of this novel virus, vaccine development for COVID-19 seems to be very challenging. However, with the accumulation of more knowledge about the virus and the efforts of global scientific cooperation, the covid-19 vaccine will be successfully developed, and the COVID-19 pandemic will eventually be controlled.