Humoral and cellular responses to SARS-CoV-2 variants after ancestral COVID-19 vaccines in people with HIV and lung transplant recipients.

OBJECTIVES

Immunocompromised hosts have reduced immune responses to COVID-19 vaccination, and more severe disease. Antibody responses correlate with protection but markers of immunity vary across a spectrum of immunocompromise. We compared serologic and cellular responses following Ancestral COVID-19 vaccines in healthy controls (HC), people with HIV (PWH) and lung transplant (LTx) recipients.

METHODS

Anti-spike receptor binding domain (RBD) IgG, neutralising antibodies (nAb) and T-cell responses were assessed one-month post-dose 2 and dose 3 of Ancestral COVID-19 vaccination in HC, PWH and LTx. NAb responses to Ancestral, Delta and Omicron BA.2 and BA.5 variants were assessed.

RESULTS

Twenty-nine HC, 21 PWH and 12 LTx recipients were included. PWH demonstrated lower anti-RBD-IgG responses (median post-dose 3: 80.3 μg mL-1 vs 43.3 μg mL-1, P = 0.03) to mRNA COVID-19 vaccination than HC, while LTx recipients displayed diminished responses following any vaccine (15.3 μg mL-1 vs 74.0 μg mL-1, P = 0.01). Dose 3 increased anti-RBD-IgG concentrations and nAb responses in HC and PWH, though Omicron variant neutralisation was attenuated. LTx recipients mounted limited nAb responses. PWH and HC had no difference in nAb responses for Ancestral (median 1738 vs 486.2, P > 0.99) or BA.5 variants (median 34.0 vs 67.9, P > 0.99). Compared with HC, PWH and LTx demonstrated reduced frequencies of SARS-CoV-2-specific memory T cells and a reduced functional memory T-cell response in LTx.

CONCLUSION

Although Dose 3 was beneficial, LTx recipients demonstrated lower serological responses than HC, while reductions were modest in PWH. Immunocompromised groups had reduced but detectable SARS-CoV-2-specific T-cell responses, demonstrating the utility of COVID-19 vaccination despite poorer serological responses.