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Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity., Author summary The SARS-CoV-2 virus is likely to have emerged following a cross-species jump from bats to humans in Wuhan, China at the end of 2019. As the virus has evolved to adapt to humans, new viral variants have emerged that incorporate mutations in the “spike” gene. The spike protein is expressed on the surface of the virus, it facilitates entry into human cells and is the main target of neutralising antibodies. Mutations change the shape of the spike protein, preventing antibody recognition and enabling the virus to escape from the immunity induced by vaccination. Using samples collected from vaccinated people as part of the COVID-19 Deployed Vaccine Cohort Study (DOVE), we assessed the capacity of different variants (beta, kappa and delta) to evade the protective immune response in recipients of the Astra Zeneca ChAdOx1 and Pfizer BNT162b2 vaccines, both of which are based on the early Wuhan virus spike gene. We noted a reduction in neutralisation of both the beta and delta variants by vaccine sera from recipients of both vaccines. While vaccines remain highly effective at preventing severe infection and death, ongoing monitoring of vaccine effectiveness is indicated as the virus continues to evolve over time, especially in vulnerable groups.

Arboviruses such as bluetongue virus (BTV) replicate in arthropod vectors involved in their transmission between susceptible vertebrate-hosts. The “classical” BTV strains infect and replicate effectively in cells of their insect-vectors (Culicoides biting-midges), as well as in those of their mammalian-hosts (ruminants). However, in the last decade, some “atypical” BTV strains, belonging to additional serotypes (e.g., BTV-26), have been found to replicate efficiently only in mammalian cells, while their replication is severely restricted in Culicoides cells. Importantly, there is evidence that these atypical BTV are transmitted by direct-contact between their mammalian hosts. Here, the viral determinants and mechanisms restricting viral replication in Culicoides were investigated using a classical BTV-1, an “atypical” BTV-26 and a BTV-1/BTV-26 reassortant virus, derived by reverse genetics. Viruses containing the capsid of BTV-26 showed a reduced ability to attach to Culicoides cells, blocking early steps of the replication cycle, while attachment and replication in mammalian cells was not restricted. The replication of BTV-26 was also severely reduced in other arthropod cells, derived from mosquitoes or ticks. The data presented identifies mechanisms and potential barriers to infection and transmission by the newly emerged “atypical” BTV strains in Culicoides.

INTRODUCTION The emergence of three lethal coronaviruses in Jennifer Meadows, Michael Dong, Ola Wallerman, Vikki Marinescu & Kerstin Lindblad-Toh ingår i gruppen Zoonomia Consortium

A Correction to this paper has been published: https://doi.org/10.1038/s41564-021-00869-0 .

Genetic exchange by a process of genome-segment ‘reassortment’ represents an important mechanism for evolutionary change in all viruses with segmented genomes, yet in many cases a detailed understanding of its frequency and biological consequences is lacking. We provide a comprehensive assessment of reassortment in bluetongue virus (BTV), a globally important insect-borne pathogen of livestock, during recent outbreaks in Europe. Full-genome sequences were generated and analysed for over 150 isolates belonging to the different BTV serotypes that have emerged in the region over the last 5 decades. Based on this novel dataset we confirm that reassortment is a frequent process that plays an important and on-going role in evolution of the virus. We found evidence for reassortment in all ten segments without a significant bias towards any particular segment. However, we observed biases in the relative frequency at which particular segments were associated with each other during reassortment. This points to selective constraints possibly caused by functional relationships between individual proteins or genome segments and genome-wide epistatic interactions. Sites under positive selection were more likely to undergo amino acid changes in newly reassorted viruses, providing additional evidence for adaptive dynamics as a consequence of reassortment. We show that the live attenuated vaccines recently used in Europe have repeatedly reassorted with field strains, contributing to their genotypic, and potentially phenotypic, variability. The high degree of plasticity seen in the BTV genome in terms of segment origin suggests that current classification schemes that are based primarily on serotype, which is determined by only a single genome segment, are inadequate. Our work highlights the need for a better understanding of the mechanisms and epidemiological consequences of reassortment in BTV, as well as other segmented RNA viruses., Author Summary Segmented viruses have genomes that are separated into multiple segments, comparable to chromosomes in higher organisms. When two segmented viruses of the same species infect the same cell, their progeny may incorporate segments picked up from the “parental” viruses. This process is called “reassortment” and represents an important way for segmented viruses to evolve. Whereas reassortment has received a lot of attention in certain segmented viruses, especially influenza A, its frequency and biological consequences remain poorly understood for most of the others. Here, we present a comprehensive analysis of the reassortment patterns in bluetongue virus, an important pathogen of livestock, during its repeated emergence in Europe in recent decades. We confirm earlier reports that reassortment is common and can involve segments derived from live vaccines used to control outbreaks. However, the mixing of viral genomes is not strictly random and reassortment is commonly followed by novel adaptive changes in the progeny virus. This points to important functional links (paired associations) between certain segments. Our findings have important implications for the classification and control of segmented viruses and generate new insights and hypotheses about the biological interactions among different parts of the bluetongue virus genome.