Broad-spectrum pan-genus and pan-family virus vaccines

Abstract

Although the development and clinical application of SARS-CoV-2 vaccines during the COVID-19 pandemic demonstrated unprecedented vaccine success in a short time frame, it also revealed a limitation of current vaccines in their inability to provide broad-spectrum or universal protection against emerging variants. Broad-spectrum vaccines, therefore, remain a dream and challenge for vaccinology. This review will focus on current and future efforts in developing universal vaccines targeting different viruses at the genus and/or family levels, with a special focus on henipaviruses, influenza viruses, and coronaviruses. It is evident that strategies for developing broad-spectrum vaccines will be virus-genus or family specific, and it is almost impossible to adopt a universal approach for different viruses. On the other hand, efforts in developing broad-spectrum neutralizing monoclonal antibodies have been more successful and it is worth considering broad-spectrum antibody-mediated immunization, or "universal antibody vaccine," as an alternative approach for early intervention for future disease X outbreaks.

Keywords: antibody vaccine; broad-spectrum vaccine; disease X; passive immunization; ring vaccination; universal vaccine.

Figure 1

Developmental stages for universal vaccine candidates (A–C) (A) Clinical development of henipavirus vaccines (A), influenza virus (B), and SARS-CoV-2 (C), (adapted from Biorender). (A) #Based on PubMed search criteria, “Nipah Hendra or Henipa vaccine, other animals, non-review, cross-reactive.” (B) ^{^}Based on PubMed search criteria, “universal influenza vaccine human” and filter for clinical trial phase. ^∗Based on WHO pandemic influenza vaccine report (October 2022). =Based on Clinicaltrials.gov search criteria, “influenza vaccine.” (C) ∼Based on covid19.trackvaccines.org (December 2022). +Based on Clinicaltrials.gov search criteria, “variant COVID vaccine” and filter for clinical trial phase. (D) Multivalent vaccines represent a fraction of registered clinical trials (from A–C).

Figure 2

Sequence conservation among different influenza virus clades (A) Definition of influenza breadth based on HA phylogeny. The tree was built with IQ-TREE2 (default parameters with automatic model selection) using HA (HE) protein sequences obtained from the Influenza Virus Database. Human influenza viruses as indicated (black: subtype endemic to humans, green: (H2, B/Yam) previously in humans, red: spill over infections from zoonotic sources). (B) Amino acid sequence conservation based on sequence alignment (CLUSTALWjp) of proteins (from https://www.ncbi.nlm.nih.gov/genomes/FLU/Database/nph-select.cgi?go=genomeset) of H1N1 2009 pandemic (A/California/04/2009) versus prototypic virus strains: for Pan (B/Vic, B/Brisbane/60/2008), for Pan A (H3N2, A/Alaska/03/2021), for group 1 (H5N1, A/Indonesia/5/2005), for subtype (H1N1, A/Alabama/01/2020).

Figure 3

Antigenic cartography of SARS-related coronaviruses Antigenic map was generated by the neutralization titers 50%. The antigenic distance between SARS-CoV-2 and SARS-CoV-1 or Omicron BA.1 in individuals who had been vaccinated against or infected by SARS-CoV-2 (left) and SARS survivors who had received 2 doses of SARS-CoV-2 mRNA vaccines (right). One antigenic unit indicates 2-fold dilution in titer.

Figure 4

Strategies for developing pan-sarbecovirus vaccines Graphical illustration of the vaccination strategy that elicits pan-sarbecovirus immunity. This includes mosaic nanoparticle, cocktail of inactivated virus particles, chimeric spike mRNA vaccine, and sequential cross-clade boosting.