A vaccine based on the yeast-expressed receptor-binding domain (RBD) elicits broad immune responses against SARS-CoV-2 variants

Development of safe and efficient vaccines is still necessary to deal with the COVID-19 pandemic. Herein, we reported that yeast-expressed recombinant RBD proteins either from wild-type or Delta SARS-CoV-2 were able to elicit immune responses against SARS-CoV-2 and its variants. The wild-type RBD (wtRBD) protein was overexpressed in Pichia pastoris, and the purified protein was used as the antigen to immunize mice after formulating an aluminium hydroxide (Alum) adjuvant. Three immunization programs with different intervals were compared. It was found that the immunization with an interval of 28 days exhibited the strongest immune response to SARS-CoV-2 than the one with an interval of 14 or 42 days based on binding antibody and the neutralizing antibody (NAb) analyses. The antisera from the mice immunized with wtRBD were able to neutralize the Beta variant with a similar efficiency but the Delta variant with 2~2.5-fold decreased efficiency. However, more NAbs to the Delta variant were produced when the Delta RBD protein was used to immunize mice. Interestingly, the NAbs may cross react with the Omicron variant. To increase the production of NAbs, the adjuvant combination of Alum and CpG oligonucleotides was used. Compared with the Alum adjuvant alone, the NAbs elicited by the combined adjuvants exhibited an approximate 10-fold increase for the Delta and a more than 53-fold increase for the Omicron variant. This study suggested that yeast-derived Delta RBD is a scalable and an effective vaccine candidate for SARS-CoV-2 and its variants.

Longevity of vaccine protection: Immunological mechanism, assessment methods, and improving strategy

Vaccination represents one of the most important achievements in modern medicine. During the era of COVID‐19 pandemic, the successful vaccination for SARS‐COV‐2 is the major hope to bring the society back to normal. However, although vaccines, such as for smallpox and poliomyelitis, can trigger life‐long protection in individuals and help to generate the herd immunity resulting in the eradication of pathogens, other vaccines, with seasonal influenza vaccine as a case in point, are unable to induce sustained immunity so that repeated vaccination is required. As most vaccines were developed empirically, the immunological mechanism underlying the longevity of vaccine‐induced protection remains only partially understood. In this review, we first describe vaccine‐induced humoral immune response in which long‐lived plasma cells and memory B cells are produced. We then summarise methods using immunological correlates of protection to assess the longevity of vaccine efficacy and provide the evidence and knowledge for the duration of protection by current vaccines. Last, we discuss rationale and strategies to improve the duration of vaccine protection by targeting vaccine immunogenicity, antibody affinity, avidity and prime‐boost scheme.

High levels of soluble CD25 in COVID-19 severity suggest a divergence between anti-viral and pro-inflammatory T-cell responses.

OBJECTIVES: We aimed to gain an understanding of the paradox of the immunity in COVID-19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. METHODS: A total of 280 hospitalised patients with COVID-19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single-cell RNA sequencing (scRNA-seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID-19 patients. RESULTS: The levels of soluble CD25 (sCD25), IL-6, IL-8, IL-10 and TNF-α were higher in severe COVID-19 patients than non-severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV-infected mice with high levels of sCD25 demonstrated insufficient anti-viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD-1 with pro-inflammatory potential. The counterpart human CD25+PD-1+ T cells were expanded in BALF of COVID-19 patients with severe disease compared to those with modest disease. CONCLUSION: These results suggest that high levels of sCD25 in COVID-19 patients probably result from insufficient anti-viral immunity and indicate an expansion of pro-inflammatory T cells that contribute to disease severity.