Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant

Abstract

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

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

“…Fold-changes against subsequent variants tested are presented as relative to the virus used for infection (Figure 4). Data for hamsters infected with ancestral, BA.1, BA.4 and BA.5.2.1 are described previously but also presented here [27,28]. As our results from the human data indicated that the FCS substitution in the BA.2.86 -A virus did not affect neutralisation titres, repeat assays with these volume-limited sera were not performed with the second virus.…”

“…Sera collected at day 27 post-infection from hamsters exposed to ancestral virus (n=6) and BA.1 (n=5) or day 28 post-infection with BA.4 (n=6) and BA.5.2.1 (n=6). These hamster sera were generated as previously described [27, 28]. Sera was collected from hamsters infected with XBB1.16 and XBB.2.3 (n=6 per variant) with a target dose of 1×10 4 FFU/200 µL via intranasal instillation (method previously described [27, 28]).…”

“…These hamster sera were generated as previously described [27, 28]. Sera was collected from hamsters infected with XBB1.16 and XBB.2.3 (n=6 per variant) with a target dose of 1×10 4 FFU/200 µL via intranasal instillation (method previously described [27, 28]). Blood samples were collected during necropsy at 28 days post infection.…”

“…Sera collected at day 27 post-infection from hamsters exposed to ancestral virus (n=6) and BA.1 (n=5) or day 28 post-infection with BA.4 (n=6) and BA.5.2.1 (n=6). These hamster sera were generated as previously described[27,28]. Sera was collected from hamsters infected with XBB1.16 from summary of geometric mean neutralisation titres from a focus-reductions assay (FRNT) for a panel of sera taken from Syrian hamsters (n=6) at day 28 post a single challenge with the XBB.2.3 SARS-CoV-2 variant.…”

Global variation in prior exposure shapes antibody neutralization profiles of SARS-CoV-2 variants up to BA.2.86

“…SARS-CoV-2 variants were isolated and propagated on Vero/hSLAM cells (ECACC 04091501) before being subjected to quality control checks as previously described ( (Coombes, Bewley, Le Duff, Hurley, et al 2023). Briefly, titrations were performed using a focus-forming assay with immunostaining for nucleocapsid to visualize foci (Ryan et al 2023). Sighting for each variant into the Focus Reduction neutralization Test (FRNT) to calculate dilution at which a median of 130 foci could be counted in non-neutralized control wells was performed.…”