COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

Abstract

Patients with cancer have a higher risk of severe coronavirus disease (COVID-19) and associated mortality than the general population. Owing to this increased risk, patients with cancer have been prioritized for COVID-19 vaccination globally, for both primary and booster vaccinations. However, given that these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, and the extent of humoral and cellular immune responses in these patients, as well as the risks of vaccine-related adverse events. In this Review, we summarize the current knowledge generated in studies conducted since COVID-19 vaccines first became available. We also highlight critical points that might affect vaccine efficacy in patients with cancer in the future.

Fig. 1. Induction of immune responses by currently available COVID-19 vaccines.

a | mRNA vaccines (including BNT162b2 and mRNA-1273) are delivered to bystander cells inside lipid nanoparticles at the injection site. The mRNA encodes a modified version of the spike protein which is translated by ribosomes, secreted by the bystander cell and in turn taken up and processed by antigen-presenting cells (APCs; in this image dendritic cells (DCs)). b | Adenoviral vector vaccines (including ChAdOx1, Ad26.COV2.S and Sputnik V) contain cDNA encoding a full-length spike protein. While most vaccines use the same adenoviral vector for each vaccine dose, Sputnik V uses two different human adenoviral vectors to prevent immune reactions against the vector. cDNA is transported to the nucleus where it is transcribed to mRNA and subsequently translated into spike protein in the cytoplasm. This spike protein is then taken up and processed by APCs. c | Protein-based vaccines (including NVX-CoV2373) consist of the spike protein and an adjuvant which is directly processed by APCs. d | Attenuated virus vaccines (including CoronaVac and BBIBP-CorV) contain whole inactivated virus particles and adjuvants which are directly processed by APCs. In the lymph nodes, APCs will present processed peptides and thus activate T cell responses (including CD4⁺ and CD8⁺ responses) and B cell responses, and in turn antibody responses. The precise immune reaction and strength of activation depends on the vaccine type. Detailed information for each vaccine is summarized in Supplementary Table 1.

Fig. 2. Overview of reported COVID-19 vaccine prime-boost schemes and clinical efficacies.

a | Reported prime boost regimens and clinical efficacy in individuals without cancer. ‘Efficacy of boost’ data are from refs^,. b | Reported prime boost regimens and clinical efficacy in patients with cancer. Primary vaccination (prime) usually consists of two vaccine doses (except for Ad26.COV2.S) which are administered at intervals of variable length from 21 days to 3 months. Vaccine efficacy (VE) in these studies is defined as the prevention of symptomatic COVID-19. The strength of serological responses is summarized with arrows indicating a moderate (one arrow) or strong (two arrows) response. An additional booster dose is administered 2 to 6 months after completion of prime vaccination. Boosts can either be homologous (same vaccine type) or heterologous (different vaccine type) and consist of one dose. Additional booster doses either designed against wild-type or with variant-specific designs are expected to become available in the next months (and in some countries are already available for patients with a compromised immune system), although the clinical efficacy and the optimal regimens need to be determined. ^aSlightly varying responses reported from two different studies.