¿p#1 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes COVID-19, remains a major global health threat. T cell immunity, particularly CD8 + cytotoxic T lymphocytes (CTLs), is essential for viral clearance and long-term protection. This study focused on CTL epitopes restricted by HLA-A11:01 and HLA-A02:01, using bioinformatic predictions and HLA transgenic mouse models to identify and validate immunodominant epitopes from SARS-CoV-2 structural proteins (S, E, M, N). Results showed strong correlation between predicted immunogenicity scores (NetMHCpan, NetCTLpan) and actual CTL responses for HLA-A11:01-restricted epitopes. HLA-A02:01-restricted epitopes showed more variable correlation, likely due to antigen processing differences and TCR repertoire diversity. Notably, 21 epitopes were highly conserved across twelve major SARS-CoV-2 variants, suggesting their potential as universal vaccine targets. Significant variability in CTL responses to selected epitopes was observed among COVID-19-recovered individuals, possibly influenced by antigen presentation efficiency. This supports epitope fingerprinting—a strategy that categorizes individuals based on their T cell memory breadth and intensity, with potential for enhancing vaccine efficacy assessments and identifying those with strong immune memory at reduced reinfection risk. This study provides experimental and theoretical insights supporting epitope-based SARS-CoV-2 vaccine optimization and targeted immunization strategies.

Over three years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variants. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation. Thus, the acquired immunity established among humans is complicated, and there is a lack of understanding within a panoramic vision. Here, we provide the special characteristics of the cellular and humoral responses in 2-year convalescents after inactivated vaccines, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and NAb, but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, inoculation with inactivated vaccine fueled the NAb to BA.1, BA.2, BA.4, and BA.5 in 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed in 2-year convalescents after inoculation. The study provides insight into the complicated features of human acquired immunity to SARS-CoV-2 and variants in the real world, indicating that promoting vaccine inoculation is essential for achieving herd immunity against emerging variants, especially in convalescents.

A male passenger arriving at Nanning Wuxu Airport in Guangxi on an international flight from Jakarta, Indonesia, was found to be positive for SARS-CoV-2 nucleic acid on a routine test at the airport on June 8 2021. The passenger was sent to Fourth People’s Hospital of Nanning immediately for further isolation and observation. On the day of admission, the test for SARS-CoV-2 nucleic acid of nasopharyngeal swabs, pharyngeal swabs and sputum specimens were positive (CT values of N gene and ORF1ab gene were between 20 and 30). After 8 weeks of hospitalization, the patient’s test for SARS-CoV-2 nucleic acid of all specimens turned to negative. We isolated a SARS-CoV-2 variant strain from the nasal swab of the patient, and then we found that the genome sequence of the variant strain had 13 base deletions and 38 nucleotide mutations compared with that of the Novel Coronavirus Wuhan strain after sequencing, comparison and analysis. The deletions and mutations of the variant strain resulted in four amino acid deletions and 30 amino acid mutations. Furthermore, we found that the variant strain was similar to those from Indonesia, South Korea and The United Kingdom after conducting BLAST analysis on GISAID platform, among them, hCOV-19 /Indonesia/ Ji-ITD-43591N /2021 was the most similar, with 99.98% similarity and only 8 base differences. The maximum likelihood phylogenetic tree was constructed taking the Wuhan strain as the root and including most the reference sequence contained most of the epidemic strains. The result showed that the strains isolated in our laboratory belonged to Delta strain.