Kempster, S. | Search bioRxiv

bioRxiv2023

Evaluation of the neutralising antibody response in human and hamster sera against SARS-CoV-2 variants up to and including BA.2.86 using an authentic virus neutralisation assay

New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an "arms race" with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including JN.1. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three doses of an ancestral vaccine but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). In our recent studies, however, the JN.1 VOI was found to be significantly more resistant to neutralisation by antibodies from those who had received the ancestral/BA.1 bivalent boost. Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The recent contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.

cell biology↗

bioRxiv2021

SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge

The Covid-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus-like mimics, based on expression of the structural proteins of a target virus that can stimulate strong neutralizing antibody responses. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co-expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous [~]100nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, a non-adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein, reduced virus shedding following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant) and protected against disease associated weight loss. Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data, using an established and scalable technology, suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.

microbiology↗