SARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals

• Published in: Nature communications Vol. 15; no. 1; p. 3077
• Main Authors: Urschel, Rebecca, Bronder, Saskia, Klemis, Verena, Marx, Stefanie, Hielscher, Franziska, Abu-Omar, Amina, Guckelmus, Candida, Schneitler, Sophie, Baum, Christina, Becker, Sören L., Gärtner, Barbara C., Sester, Urban, Martinez, Leonardo, Widera, Marek, Schmidt, Tina, Sester, Martina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 631/250/1619/554; 631/250/2152/1566/1571; 631/250/2152/2153/1291; 631/250/590/2293; 692/53/2423; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Breakthrough Infections; CD4 antigen; CD8 antigen; COVID-19; COVID-19 - prevention & control; Humanities and Social Sciences; Humans; Humoral immunity; Immunity; Immunity, Humoral; Immunogenicity; Immunoglobulin G; Infections; Lymphocytes; Lymphocytes T; mRNA; multidisciplinary; Neutralizing; Observational studies; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccines; Vaccines, Combined; Viral diseases; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47429-8

Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection ( n  = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals ( n  = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections. Prior infection or exposure to SARS-CoV-2 may influence immunogenicity and effectiveness of subsequent vaccination to new strains of virus. Here the authors show that immunogenicity of a BA.4/5 mRNA vaccine differed in recipients depending on whether they had been exposed to or infected with an earlier strain of virus.