Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay

Abstract

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 BA.2.86. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three vaccines but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). 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 most 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.

Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023

“…During 2023, the BA.2.86 lineage with an unusually large number of additional mutations in the spike protein has been a cause of concern. Whereas serum neutralisation escape was not found to be increased over previously circulating strains [2][3][4][5][6][7][8][9][10][11][12][13], the derived JN.1 sublineage with an additional substitution in the spike protein (L455S) currently shows stronger increase in circulation than BA.2.86 worldwide [14,15].…”

Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera

“…Our merged human-hamster primary infection map positions BA.4/BA.5 and JN.1 in a cluster with newer XBB Omicron variants, suggesting shared epitopes. Previous studies have included limited number of samples or no sera raised against newer variants 15-17,26,39,49 . By including additional single exposure hamster sera for BA.1, BA.4/BA.5, XBB variants and JN.1, our study helps to increase resolution in this region of antigenic space.…”

Immunogenicity and safety of an Omicron XBB.1.16 adapted vaccine for COVID-19: Interim results from a randomized, controlled, non-inferiority clinical trial

“…In addition to planned immunogenicity assessments a virus neutralization assay (VNA) was conducted in a random subset of serum samples to compare humoral immune response between vaccine arms against the Omicron JN.1. 21 22…”