In a recent study posted to bioRxiv* preprint server, researchers assessed the neutralization efficacy of a self-amplifying ribonucleic acid (saRNA) vaccine targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein against reinfection among hamsters with prior vaccination or infection.
Study: Omicron breakthrough infections in vaccinated or previously infected hamsters. Image Credit: CREATIVE WONDER/Shutterstock
*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
The second and third years of the coronavirus disease 2019 (COVID-19) pandemic have been marked by the repeated emergence and replacement of SARS-CoV-2 variants, such as the emergence of the Omicron variant, which replaced the Delta variant.
The authors of the present study previously showed that two doses of saRNA-S protein vaccine conferred protection against the Wuhan-hu-1/D614G and Alpha strains among vaccinated hamsters.
About the study
In the present study, researchers extended their previous analysis by assessing the protection conferred by double saRNA vaccination and prior Omicron BA.1 infection against Delta or Omicron BA.2 reinfections in hamsters.
Groups of hamsters (n=16 per group) were vaccinated with prime and boost doses of the saRNA S vaccine or a control vaccine which encoded human immunodeficiency virus (HIV) glycoprotein (gp) 120 (saRNA-HIV). Two weeks post-boost, hamster sera were obtained, following which the hamsters were challenged via direct contact exposure.
Hamsters were intranasally infected with 100 plaque-forming units (PFU) of Omicron BA.1 or Delta. The animals shed SARS-CoV-2 in their nasal wash after the first day post-infection (dpi). The vaccinated hamsters were co-housed with infected donor hamsters at one dpi. Therefore, every cage housed a donor, a saRNA-S vaccinee, and a control saRNA-HIV vaccinee animal. Pseudovirus neutralization assays were performed with sera obtained at 14 dpi to assess neutralizing activity against the SARS-CoV-2 variants.
Subsequently, groups of hamsters (n=4 per group) were infected with 100 PFU viral isolates of D614G strain and the Alpha, Delta, Omicron BA.1, BA.2 variants or were mock-infected (controls). The potential for airborne SARS-CoV-2 transmission by the infected hamsters was assessed. Plaque assays were also performed to assess plaque formation by SARS-CoV-2 variants on cultured cells.
Further, the in vivo findings among hamsters were compared to human antibody titers of antisera obtained from hospitalized individuals infected by D614G (n=9), Alpha (n=9), Delta (n=12), or BA.1 (n=16). The neutralizing antibody titers among individuals who developed SARS-CoV-2 breakthrough infections after double saRNA S vaccination were assessed.
Results
Double saRNA vaccination based on the D614G S ameliorated weight loss and reduced viral loads following Delta infection but had a minimal effect against BA.1. Prior D614G or Alpha infection was partially protective against Omicron BA.1. All Delta-infected hamsters exposed to Omicron developed reinfections, although SARS-CoV-2 shedding among them was lower.
Hamsters vaccinated with saRNA-S demonstrated robust D614G neutralization but a two-fold decrease and 13-fold decrease in neutralizing titers against Delta and BA.1, respectively. Sera of saRNA-S vaccinated hamsters infected by BA.1, and BA.2 demonstrated marginally lower neutralizing titers than against D614G and Delta, lowest against BA.1.
SARS-CoV-2 envelope (E) gene analysis showed SARS-CoV-2 infection in all sentinel hamsters; however, the viral load and viral RNA in the nasal wash of saRNA-S vaccinated and Delta-infected hamsters were substantially lower than controls. Contrastingly, SARS-CoV-2 load in the nasal wash of Omicron-infected animals was minimally affected by vaccination and only lower than controls at five dpi. Among all infected hamsters, BA.1 neutralization titers in the nasal washes were the lowest. All naïve sentinel hamsters acquired BA.1 infection from co-housed donors, and their nasal wash demonstrated high BA.1 shedding.
Plaque assays showed that the plaque counts did not significantly differ between naïve sentinel hamsters and Delta-infected hamsters. This was indicative of their potential to support the onward SARS-CoV-2 airborne transmission. In contrast, after BA.2 exposure, the directly infected donor hamsters, immunonaïve sentinel hamsters, and the BA.1-infected sentinel hamsters emitted detectible SARS-CoV-2 particles in the air. This indicates that prior Omicron BA.1 infection conferred partial protection against BA.2 reinfections but not Delta reinfections.
Pseudovirus neutralization assays showed paralleled in vivo and human antisera findings. Individuals who recovered following infection by earlier SARS-CoV-2 variants did not demonstrate cross-neutralization between Delta and Omicron, indicative of a large antigenic distance between Delta and Omicron.
A 120-fold-decrease and a 60-fold decrease in neutralizing antibodies against BA.1 were observed among Delta-infected and Alpha-infected individual antisera, respectively. D614G-infected individuals demonstrated a 129-fold decrease in BA.1 neutralization, which was 23-fold and 15-fold lower than those against Delta and Omicron BA.2, respectively. The findings indicate a considerable antigen distance between earlier SARS-CoV-2 variants and Omicron and between BA.1 and BA.2 in immunonaïve individuals. Delta and Omicron breakthrough infections yielded higher and broader antibody titers than after only vaccination. In comparison to homologous strain titers. a 3.5-fold drop in antibody titers was observed against Omicron BA.1 among vaccinated and Delta-infected individuals.
Conclusion
Overall, the study findings showed that double saRNA vaccination conferred substantially low immune protection against Omicron BA.1, and hamsters previously infected with pre-Omicron variants could develop Omicron reinfections via airborne transmission. Further, Delta and Omicron infections did not confer cross-protective immunity in hamsters.
*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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