Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant

Abstract

PURPOSE To examine COVID-19 mRNA vaccine–induced binding and neutralizing antibody responses in patients with non–small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis

“…Studies conducted in populations defined by particular diseases or treatment (such as autoimmune conditions treated with immunosuppressive agents, myeloma, lung cancer and dialysis) have provided mixed results relating to the impact of ethnicity on immunogenicity of SARS-CoV-2 vaccine. 16 , 17 , 18 , 19 , 20 , 21 A recent study reporting findings from a large cohort of UK healthcare workers (HCWs) found higher SARS-CoV-2 anti-spike titres in ethnic minority vaccinees than in their White counterparts, 22 which contrasts with another UK HCW study which found lower peak anti-spike antibody titres in Black HCWs compared to White HCWs and did not find differences between the White and Asian groups. 23 A large UK observational study in the general population found South Asians vaccinees to have higher combined IgG, A and M titres against SARS-CoV-2 than those from White groups.…”

Serological Response to SARS-CoV-2 after COVID-19 Vaccination in Lung Cancer patients: Short Review

“…Articles that focused only on LC patients showed that COVID-19 mRNA and viral vectorbased vaccines can safely generate humoral immune responses in these patients, albeit at somewhat diminished levels compared to those in the general population. Out of the nine articles that specifically examine vaccine immunogenicity in LC patients, six demonstrate significant differences in median titers following the primary vaccination series when compared to HC data [29][30][31][33][34][35]. The variety of emerging and still-evolving Omicron variants of SARS-CoV-2, with the ability to overcome primary vaccination-induced immunity, present significant new threats to LC patients.…”

“…IgG titers were maintained over time with low infection and reinfection rates with a mild clinical course. None of the reports by Valanparambil et al [33], Mack et al [32], and Hernandez et al [28] observed differences in serologic responses as a result of cancer treatment in LC patients, but with significant heterogeneity in treatment modalities, were not necessarily powered to do so.…”

“…This study showed that 25% of the patients analyzed for neutralization activity had a titer level lower than the threshold associated with 50% protection (20% of the GMT geometric mean neutralizing titer [37]. In order to test whether healthy vaccine recipients and NSCLC patients had neutralizing antibodies against the parental virus and VOC in response to the first doses of mRNA vaccines, Valanparambil et al [33] used a live virus neutralization assay. They found that 25% of patients had lower NT Ab titers than controls against WT and that a significant fraction of LC patients (18%) failed to generate detectable NT Ab titers.…”

Longitudinal Analyses of COVID-19 Vaccination in Patients With Lung Cancer: Antibody Responses and Variant-Specific Neutralization

“…In the article accompanying this editorial, Valanparambil et al 6 performed longitudinal studies of anti–severe acute respiratory syndrome coronavirus 2 SPIKE protein titers and the ability of these antibodies to neutralize authentic virus in patients with lung cancer after vaccination and boost with a mRNA vaccine and although 75% of patients mounted a good anti-viral immune response, 25% failed to generate an adequate immune response after initial vaccination, raising questions about causes of this failure and optimal approaches to vaccinate patients with lung cancer. This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients.…”