Oral Presentation 12th Australasian Virology Society Meeting 2024

Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals (#45)

Haogao Gu 1 , Ahmed Abdul Quadeer 2 3 , Pavithra Krishnan 1 , Daisy Ng 1 , Lydia Chang 1 , Liu Gigi 1 , Samuel Cheng 1 , Tommy Lam 1 4 5 , Malik Peiris 1 4 6 , Matthew McKay 2 3 , Leo Poon 1 4 6
  1. School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  2. Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC, Australia
  3. Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia
  4. Centre for Immunology & Infection, Hong Kong Science and Technology Park, Hong Kong SAR, China
  5. Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, Hong Kong SAR, China
  6. HKU Pasteur Research Pole, School of Public Health,, LKS Faculty of Medicine, Hong Kong SAR, China

Both viral and host factors influence SARS-CoV-2 evolution, but our understanding of lineage-specific and vaccination-related mutations within individuals remains limited. In our work [1], we analyzed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples, collected in Hong Kong between mid-2020 and 2022, across various viral lineages to examine within-host diversity patterns under different conditions, including vaccine breakthrough infections. Our analysis revealed that in unvaccinated individuals, Variants of Concern (VOCs) Alpha, Delta, and Omicron exhibited higher within-host diversity compared to non-VOC SARS-CoV-2. These VOCs were subject to neutral to purifying selection at the whole-genome level. Importantly, breakthrough infections in individuals vaccinated with two or three doses of Comirnaty or CoronaVac vaccines did not lead to increased non-synonymous mutations or alter selection pressure direction. Furthermore, vaccine-induced antibody or T cell responses showed no significant impact on SARS-CoV-2 sequence diversification within hosts. These findings suggest that vaccination does not enhance SARS-CoV-2 protein sequence space exploration and may not contribute to the emergence of new viral variants.

  1. Gu, H. et al. Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals. Nat Commun 14, 1793 (2023).