Construction of a potent pan-vaccine based on the evolutionary tendency of SARS-CoV-2 spike protein. (preprint)

SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.

Co-infection of influenza A virus enhances SARS-CoV-2 infectivity (preprint)

The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic may raise a potentially severe threat to public health. However, little is known about the consequences of the co-infection of influenza A virus (IAV) and SARS-CoV-2. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Intriguingly, such enhancement of SARS-CoV-2 infectivity was only seen under co-infection with IAV but not with several other viruses including Sendai virus, human rhinovirus, human parainfluenza virus, human respiratory syncytial virus, or human enterovirus 71. IAV infection rather than interferon signaling induced elevated expression of ACE2 essential for such enhancement of SARS-CoV-2 infectivity. Remarkably, we further confirmed that the pre-infection of IAV indeed resulted in an increased SARS-CoV-2 viral load and more severe lung damage in hACE2-transgenic mice. This study illustrates that the co-infection of IAV aggravates SARS-CoV-2 infection and disease severity, which in turn suggests that preventing the convergence of flu season and COVID-19 pandemic would be of great significance.