Willett, B. | bioRxiv Science

bioRxiv2022

SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity

Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralisation responses against SARS-CoV-2Wuhan, SARS-CoV-2, SARS-CoV-2{delta} and SARS-CoV-2o pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2 or SARS-CoV-2{delta}, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design. Author SummaryNeutralising antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralising antibodies is a protein called Spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting-in some cases-people that had been previously infected or vaccinated. Since the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralising antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

microbiology↗

bioRxiv2021

Molecular epidemiology of peste des petits ruminants virus emergence in critically endangered Mongolian saiga antelope and other wild ungulates

Peste des petits ruminants virus (PPRV) causes disease in domestic and wild ungulates, is the target of a global eradication programme and threatens biodiversity. Understanding the epidemiology and evolution of PPRV in wildlife is important, but hampered by the paucity of wildlife-origin PPRV genomes. In this study, full PPRV genomes were generated from three Mongolian saiga antelope, one Siberian ibex and one goitered gazelle from the 2016-2017 PPRV outbreak. Phylogenetic analysis showed that for Mongolian and Chinese PPRV since 2013, the wildlife and livestock-origin genomes were closely related and interspersed. There was strong phylogenetic support for a monophyletic group of PPRV from Mongolian wildlife and livestock, belonging to clade of lineage IV PPRV from livestock and wildlife from China since 2013. Discrete diffusion analysis found strong support for PPRV spread into Mongolia from China and phylogeographic analysis indicated Xinjiang Province as the most likely origin, although genomic surveillance for PPRV is poor and lack of sampling from other regions could bias this result. Times of most recent common ancestor (TMRCA) were June 2015 (95% HPD: August 2014 - March 2016) for all Mongolian PPRV genomes and May 2016 (95% HPD: October 2015 - October 2016) for Mongolian wildlife-origin PPRV. This suggests that PPRV was circulating undetected in Mongolia for at least six months before the first reported outbreak in August 2016, and that wildlife were likely infected before livestock vaccination began in October 2016. Finally, genetic variation and positively-selected sites were identified that might be related to PPRV emergence in Mongolian wildlife. This study is the first to sequence multiple PPRV genomes from a wildlife outbreak, across several host species. Additional full PPRV genomes and associated metadata from the livestock-wildlife interface are needed to enhance the power of molecular epidemiology, support PPRV eradication and safeguard the health of the whole ungulate community. Author SummaryRecent mass mortality of critically endangered Mongolian saiga antelope due to peste des petits ruminants virus (PPRV) has dramatically highlighted the threat this viral disease represents for biodiversity. The genome of viruses such as PPRV evolve fast, so virus genetic data gathered from infected animals can be used to trace disease spread between livestock and wildlife, and to determine if the virus is adapting to infect wildlife more efficiently. Here we obtained PPRV virus genomes from Mongolian wildlife and compared them with other published PPRV genomes. Using a molecular clock, we estimated that the disease was circulating in Mongolia well before it was first reported. Genetic analyses support the hypothesis of virus spread from livestock to wildlife, with genetic changes potentially helping infection in Asian wild ungulates. However, more PPR virus genomes and epidemiology data are needed from disease outbreaks in areas shared between livestock and wildlife to confirm these results and take efficient actions to safeguard the health of the whole ungulate community.

microbiology↗