SARS-CoV-2 variant B.1.1.7 caused HLA-A2 + CD8 + T cell epitope mutations for impaired cellular immune response

Here, we evaluated the immune properties of the HLA-A2 restricted CD8+ T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8+ T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8+ T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain.
In addition, these peptides could effectively induced the activation and cytotoxicity of CD8+ T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8+ T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238. Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8+ T cell responses elicited by infection of mutated strains or vaccination.

Efficacy of ChAdOx1 vaccines against SARSCoV-2 Variants of Concern Beta, Delta and Omicron in the Syrian hamster model

ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus—vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 was shown to have 74% vaccine efficacy (VE) against symptomatic disease in clinical trials and over 2.5 billion doses of vaccine have been released for worldwide use. However, SARS-CoV-2 continues to circulate and consequently, variants of concern (VoCs) have been detected, with substitutions in the S protein that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial over boosting with vaccines encoding the ancestral S protein, even though current real-world data is suggesting good efficacy against hospitalization and death following boosting with vaccines encoding the ancestral S protein.
Using the Syrian hamster model, we evaluated the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. We then investigated the efficacy of a single dose of AZD2816 or AZD1222 against the Omicron VoC. As seen previously, minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 5 days post inoculation, in contrast to lungs of control animals. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.

Impacts of the SARSCoV-2 pandemic on the global demand for exotic pets: An expert elicitation approach

  • The SARS-CoV-2 pandemic has caused immense social and economic costs worldwide. Most experts endorse the view that the virus has a zoonotic origin with the final spillover being associated with wildlife trade. Besides human consumption, wild animals are also extensively traded as pets. Information on zoonotic diseases has been reported to reduce consumer demand for exotic pets. We conducted a global survey and collected 162 responses from international experts on exotic pet trade (traders, academics, NGOs, enforcement entities) to understand how the legal and illegal trade of exotic pets is expected to be affected by the ongoing coronavirus pandemic. Our results suggest that legal purchase of exotic pets is perceived as decreasing during the first pandemic wave due to: lower availability of animals for trade, suppliers’ inability to reach consumers and social distancing measures.
  • The general perception is that in the future (i.e., next five years), both demand and supply of legally traded exotic pets are expected to either remain unchanged or decrease only temporarily. The consumer demand for illegal exotic pets is also expected to remain unchanged following the outbreak.
  • The top two challenges reported by respondents, when considering the consequences of the pandemic for the exotic pet trade, are inadequate enforcement of national regulations and increased illegal trade. Our results suggest that the negative consequences of a zoonotic outbreak may not dissuade consumers of exotic pets. Worldwide, the transit/storing conditions and lack of health screenings of traded live animals are conducive to spreading diseases.
  • Consumer demand is a key driver of trade, and enforcement of trade regulations will remain challenging, unless factors driving consumer demand are adequately incorporated in problem-solving frameworks. We emphasize the complexity of trade dynamics and the need to go beyond bans on wildlife trade. Stronger law enforcement, implemented along with initiatives dissuading consumption of wild exotic pets, are essential to sustainably satisfy the market demand.

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SARSCoV-2 Omicron-specific mRNA vaccine induces potent and broad antibody responses in vivo

The Omicron variant of SARS-CoV-2 has high transmissibility and recently been sweeping the globe, dominating new infection cases in the US and many regions in the world. Due to its extensive number of mutations, this variant has high level of immune evasion, which drastically reduced the efficacy of existing antibodies and vaccines. Thus, it is important to develop an Omicron-specific vaccine and test if it can induce immune responses against Omicron and broadly against other variants. Here, we generated an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and tested its potency of antibody induction in animals, both alone and as a booster to existing mRNA vaccine designed against the ancestral reference virus (WA-1). This Omicron-specific LNP-mRNA vaccine elicited strong and specific antibody response in vaccination-naïve mice. Consistent with recent reports, mice that received two-dose WA-1 LNP-mRNA, the one mimicking the commonly used Pfizer/Moderna mRNA vaccine administered in the general population, showed a 41-fold reduction in neutralization potency against Omicron variant as compared to WA-1 two weeks post second dose, which further reduced to background level 3.5 months post second dose.
As a booster for WA-1 mRNA vaccination, a single dose Omicron LNP-mRNA induced potent antibody response against the Omicron variant, with over 1,000-fold increase at two weeks post injection as compared to the blood samples right before booster. The Omicron-specific antibody level of the Omicron-boosted samples is numerically similar to WA-1 vaccine against WA-1 variant. This boost also elicited broader antibody responses against WA-1 and Delta variants, restoring these activities of the WA-1 vaccinated animals that also dropped over time. A consecutive second dose of Omicron LNP-mRNA 2 weeks following the first dose did not significantly increased the level of antibodies. These in vivo animal data provided a timely proof-of-concept for Omicron-specific mRNA vaccination, alone and as a booster to the existing widely-used mRNA vaccine form.

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