In a recent preprint study posted to Research Square* preprint server, researchers evaluated the efficacy of the Oxford-AstraZeneca ChAdOx1 (AZD 1222/ AZD2816) vaccine against the Omicron, Delta, and Beta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian hamsters.
Initially discovered in Wuhan, China, SARS‑CoV‑2 spread rapidly across the globe causing the coronavirus disease 2019 (COVID-19) pandemic, leading to considerable morbidity and mortality worldwide. This prompted the development of several vaccines to help protect against the infection.
The structure of the SARS‑CoV‑2 virus comprises of many glycoproteins. An alteration in these glycoproteins such as the viral receptor binding spike (S) protein reduces the neutralizing antibody titers against the virus, increasing its virulence. Multiple variants of concern (VoCs) such as the Omicron, Delta, and Beta variants have emerged as a result of these structural alterations in SARS‑CoV‑2.
ChAdOx1 is a vaccine formulated using a non-replicating, simian-isolated adenovirus as a vector. It encodes for the non-stabilized S glycoprotein of the Beta variant. Owing to an efficacy of 74% against symptomatic cases in previous trials, it was approved for use in over 170 nations, with greater than 10.4 billion doses already administered in humans.
About the study
In the present study, the researchers investigated the efficacy of the ChAdOx1 vaccine against the SARS‑CoV‑2 Omicron, Delta, and Beta VoCs in Syrian hamsters. The experiments were ethically carried out on four- to six-weeks-old hamsters divided into three groups - unvaccinated controls, a prime-only group that received a single vaccine dose, and a prime-boost group that received two vaccines doses; 100 µL each were administered intramuscularly into the posterior thighs of the hamsters.
Virus inactivation, sequencing, and propagation were performed for all samples. After the viral stocks were devoid of all single nucleotide polymorphisms (SNPs) or mycoplasma, the nasal tissues were immunized. Oropharyngeal swabs were also collected and euthanization was performed to obtain lung tissue samples. Serum samples were also collected two weeks post-vaccination and the animals were also weighed daily.
Ribonucleic acid (RNA) extracted from these swabs was subjected to quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis to detect the presence of sub-genomic viral RNA (sgRNA). The lung samples were subjected to histology and immunocytochemistry examination by a certified vet to check for any lung pathologies. Serum containing lentiviral plasmid vectors having the K417N and E484K S proteins of the Beta variant; N501Y and the E484A proteins of the Omicron variant; and the L452R protein of the Delta variant, was subjected to virus neutralization (VN) antibody titers, live VN assays, and enzyme-linked immunosorbent assay (ELISA) to detect the presence of antibodies against the virus. The amount of sgRNA on the swabs indicative of viral replication was correlated with the antibody levels in the serum, which indicates host immune surveillance.
In the prime-boost group, elevated antibody titers were detected against S proteins of all the three variants: the Delta, Omicron, and the Beta variants, whereas the antibody titers were significantly high only against mutant proteins E484K and K417N of the Beta variant in the prime-only group. However, the difference in protection against the structurally altered Omicron variant provided by the single and double dose regimens was not significant.
In both vaccinated groups, reduced viral replication, decreased viral shedding, diminished antigen staining in the alveolar bronchial epithelium cells, minimal inflammation, fluid accumulation, and broncho-interstitial pneumonia in the terminal bronchioles and alveoli were noted compared to the controls. However, the antibody titers against the Omicron and the Delta variants were low.
No significant correlation was found between the VN titer of antibodies against any S variant and sgRNA viral genome copies in swabs. These findings suggest that although vaccine administration cannot prevent infection, the shedding of viral particles is significantly reduced. In addition, no weight loss was observed in hamsters vaccinated against the Beta variant whereas the control animals demonstrated significant weight loss.
The present study findings highlight the immunogenic potential of the ChAdOx1 vaccine against spike protein mutations present in different variants of the SARS-CoV-2 virus. While the single-dose regimen confers protection, especially against the mutated Beta variant, the double dose regimen increases the robustness and efficacy of the immune system to combat other variants.
However, future research is needed to determine the effects of higher doses and different routes of administration on viral replication, to ascertain whether minute differences observed between the two vaccine regimens against the Omicron variant are pertinent and the reason for the reduction in viral shedding against the Omicron VoC in spite of low VN titers.
Research Square 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.