COVID-19 vaccine in naive individuals and cancer patients

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have been studying the immune response of COVID-19 cohorts longitudinally to characterize the nature and longevity of immune response (Rosati M, Am J Hematol: 97:E3, 2022; Rosati Frontiers Immunol 12: 793953, 2021; Thomopoulos, Viruses 1:1844; 2021; Terpos, Eur J Intern Med, 89:87,2021; Pappa, Microorganisms 9, 806, 2021; Terpos, Microorganisms. 8:1885, 2020). The analysis of natural infection is providing important information for the design of vaccine strategies. To characterize adaptive and innate immune responses in SARS-CoV2 vaccinated persons, we identified early responses to vaccination that are important in shaping both humoral and cellular protective immunity (Bergamaschi, Cell Rep 36:109504; 2021; Bergamaschi, Frontiers Immunol 3:899972, 2022). We characterized the cytokine and chemokine responses to BNT162b2 mRNA (Pfizer/BioNtech) vaccinations in antigen-naive and in previously COVID-19-infected individuals and in patients with hematological malignancies (NCT04743388). We identified a systemic signature including IL-15, IFN-gamma, IP-10/CXCL10, TNF-alpha and IL-6. Transient increases in IL-15 and IFN-gamma levels early after boost correlated with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We expanded our studies to immunocompromised individuals including patients with hematological malignancies, a population at high risk of developing severe disease upon SARS-CoV-2 infection. Protection afforded by vaccination is frequently low and the biology leading to altered vaccine efficacy is not fully understood. Overall, the patients showed heterogeneous adaptive and innate responses with lower humoral (binding and neutralizing antibodies) and reduced innate cytokine responses (IFN-gamma, IL-15 and IP-10/CXCL10 signature) to vaccination compared to naive vaccine recipients. Changes in IFN-gamma and IP-10/CXCL10 at priming vaccination and IFN-gamma, IL-15, IL-7 and IL-10 upon booster vaccination correlated with the Spike antibody magnitude and were predictive of successful antibody development. The pattern of responses described offer novel prognostic approaches for potentiating the effectiveness of COVID-19 vaccination in transplant patients with hematological malignancies. We are expanding our research of the development of adaptive and innate immune responses upon COVID-19 vaccination to other cancer cohorts.