In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

Abstract

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent history. In this review, we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus family. We will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2, MERS-CoV and the four seasonal coronaviruses (HCoV-OC43, NL63, HKU1 and 229E) in humans and the potential for future zoonotic coronaviruses. We will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine design. We will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer cross-protection. Finally, we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

Keywords: Coronavirus; Cross-protection; Cross-reactive immunity; Universal; Vaccine.

Fig. 1

Phylogeny of coronaviruses and the breadth of protection afforded by different types of vaccines. Updated vaccines containing Omicron BA.1 or later sequences of spike have been designed to offer improved single-variant protection against currently circulating strains of SARS-CoV-2 compared with licensed vaccines. Next-generation vaccines are being designed to offer broader protection, for instance, pan-variant vaccines that could target all variants of the single viral species, SARS-CoV-2; pan-subgenus vaccines that target all members of the subgenus sarbecoviruses (including also SARS-CoV-1); pan-genus vaccines that include all members of the genus β-coronavirus (further including MERS-CoV, HCoV HKU1 and OC43); pan-subfamily vaccines that target all Orthocoronavirinae (also including alpha-coronaviruses HCoV NL63 and 229E); and pan-coronavirus vaccines that target all species within the Coronaviridae family. Created with BioRender.com

Fig. 2

Graphic summary of next-generation approaches for broadly targeted and pan-coronavirus vaccines, including nanoparticle delivery; the use of mosaic antigens or serial vaccination to educate the immune system with multiple versions of a given viral protein; the use of novel regions of the virus, in particular conserved regions outside of spike; and finally, consensus sequence design or computational antigen design, to select the antigenic sequence that induces the most broadly reactive immunity. NP nucleoprotein, NSP non-structural protein, ORF open reading frame, RBD receptor binding domain, RTC replication-transcription complex. Created with BioRender.com