Immunosuppressed patients, including solid organ transplant recipients (SOTRs), developed significantly lower antibody responses and had more breakthrough infections after two doses of COVID-19 mRNA vaccines, as compared with immunocompetent individuals. The aim of this study was to characterize vaccine-induced antibody responses, including IgG binding antibodies and live virus neutralizing antibodies (NAb) against the vaccine strain and Omicron variants, BA.1 and BA.5, as well as the levels of the IgG subclasses, IgG1-4, in SOTRs. Serum samples from SOTRs were analyzed at pre-vaccination, 30-days, and 90-days following the third dose COVID-19 mRNA vaccines (D3). For several measures, antibody responses were compared with healthy controls (HC). A third dose vaccination increased anti-spike (S) IgG titers in response to the SARS-CoV-2 vaccine and Omicron variants from pre- to post-D3 in SOTRs. Anti-S IgG responses to Omicron variants, however, were significantly lower than to the vaccine strain. SOTRs also had low live virus NAb titers to the vaccine and Omicron BA.1 variant, with many individuals having no detectable NAb. The subclass-specific anti-S IgG antibodies against the SARS-CoV-2 vaccine strain predominantly consisted of IgG1, IgG3, and IgG4 in SOTRs, which resembled the subclass profiles in HC at post-D3. Together, our findings illustrate that while a booster dose of mRNA vaccine induces antibody responses, including IgG1 and IgG3, which are the dominant antiviral IgG subclasses, in SOTRs, these responses are still lower than immunocompetent individuals. Therefore, consideration should be given to different formulations and doses of COVID-19 vaccines in people with severely compromised immune systems.

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