Mary Wilson
Well-known member
(Preprint)
May 25, 2022
doi: https://doi.org/10.1101/2022.05.25.493397
Authors: Brian J. Willett1#, Ashwini Kurshan2#, Nazia Thakur3,4#, Joseph Newman3#, Maria Manali1, Grace Tyson1, Nicola Logan1, Pablo R. Murcia1, Luke B. Snell5, Jonathan D. Edgeworth5, Jie Zhou6, Ksenia Sukhova6, Gayatri Amirthalingam7, Kevin Brown7, Bryan Charleston3, Michael H. Malim2, Emma C. Thomson1, Wendy S. Barclay6, Dalan Bailey3ǂ, Katie J. Doores2ǂ and Thomas P. Peacock6ǂ
Abstract
Over the course of the pandemic variants have arisen at a steady rate. The most recent variants to emerge, BA.4 and BA.5, form part of the Omicron lineage and were first found in Southern Africa where they are driving the current wave of infection. In this report, we perform an in-depth characterisation of the antigenicity of the BA.4/BA.5 Spike protein by comparing sera collected post-vaccination, post-BA.1 or BA.2 infection, or post breakthrough infection of vaccinated individuals with the Omicron variant. In addition, we assess sensitivity to neutralisation by commonly used therapeutic monoclonal antibodies. We find sera collected post-vaccination have a similar ability to neutralise BA.1, BA.2 and BA.4/BA.5. In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralises BA.4/BA.5 poorly. Breakthrough infection with Omicron in vaccinees leads to a broad neutralising response against the new variants. The sensitivity of BA.4/BA.5 to neutralisation by therapeutic monoclonal antibodies was similar to that of BA.2. These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2. The enhanced breadth of neutralisation observed following breakthrough infection with Omicron suggests that vaccination with heterologous or multivalent antigens may represent viable strategies for the development of cross-neutralising antibody responses.
https://www.biorxiv.org/content/10.1101/2022.05.25.493397v1.full.pdf
May 25, 2022
doi: https://doi.org/10.1101/2022.05.25.493397
Authors: Brian J. Willett1#, Ashwini Kurshan2#, Nazia Thakur3,4#, Joseph Newman3#, Maria Manali1, Grace Tyson1, Nicola Logan1, Pablo R. Murcia1, Luke B. Snell5, Jonathan D. Edgeworth5, Jie Zhou6, Ksenia Sukhova6, Gayatri Amirthalingam7, Kevin Brown7, Bryan Charleston3, Michael H. Malim2, Emma C. Thomson1, Wendy S. Barclay6, Dalan Bailey3ǂ, Katie J. Doores2ǂ and Thomas P. Peacock6ǂ
Abstract
Over the course of the pandemic variants have arisen at a steady rate. The most recent variants to emerge, BA.4 and BA.5, form part of the Omicron lineage and were first found in Southern Africa where they are driving the current wave of infection. In this report, we perform an in-depth characterisation of the antigenicity of the BA.4/BA.5 Spike protein by comparing sera collected post-vaccination, post-BA.1 or BA.2 infection, or post breakthrough infection of vaccinated individuals with the Omicron variant. In addition, we assess sensitivity to neutralisation by commonly used therapeutic monoclonal antibodies. We find sera collected post-vaccination have a similar ability to neutralise BA.1, BA.2 and BA.4/BA.5. In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralises BA.4/BA.5 poorly. Breakthrough infection with Omicron in vaccinees leads to a broad neutralising response against the new variants. The sensitivity of BA.4/BA.5 to neutralisation by therapeutic monoclonal antibodies was similar to that of BA.2. These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2. The enhanced breadth of neutralisation observed following breakthrough infection with Omicron suggests that vaccination with heterologous or multivalent antigens may represent viable strategies for the development of cross-neutralising antibody responses.
https://www.biorxiv.org/content/10.1101/2022.05.25.493397v1.full.pdf