Review 1: "Antibody Response to SARS-CoV-2 mRNA Vaccine in Lung Cancer Patients: Reactivity to Vaccine Antigen and Variants of Concern"

Chetna Mangat

doi:doi:10.1162/2e3983f5.03e16a51

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern

by Rajesh M Valanparambil, Jennifer Carlisle, Susanne L. Linderman, Akil Akthar, Ralph Linwood Millett, Lilin Lai, Andres Chang, Ashley A. McCook, Jeffrey Switchenko, Tahseen H. Nasti, Manpreet Saini, Andreas Wieland, Kelly E. Manning, Madison Ellis, Kathryn M. Moore, Stephanie L. Foster, Katharine Floyd, Meredith E. Davis-Gardner, Venkata-Viswanadh Edara, Mit Patel, Conor Steur, Ajay K. Nooka, Felicia Green, Margaret A. Johns, Fiona O’Brein, Uma Shanmugasundaram, Veronika I Zarnitsyna, Hasan Ahmed, Lindsay E. Nyhoff, Grace Mantus, Michael Garett, Srilatha Edupuganti, Madhusmita Behra, Rustom Antia, Jens Wrammert, Mehul S. Suthar, Madhav V. Dhodapkar, Suresh Ramalingam, and Rafi Ahmed

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dx.doi.org

Description

AbstractPurposeWe investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants.Methods82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated.ResultsBinding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients.ConclusionsBinding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

RR:C19 Evidence Scale rating by reviewer:

Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

This is a well structured and well written manuscript. Study design, methods and results are well described. Authors cited the recent articles available and described and compared the results with existing literature in detail. Detailed analysis and graphs are impressive and easily understandable. Mean age of the NSCLC patients is 65.9 years; however, the mean age of the healthy cohort is not described in the study. We know demographic factors cannot be ignored while assessing the humoral response to vaccine as immune response from vaccine in general could be low in older population which is a well researched topic. Mean age of NSCLS patients is 65 + and humoral response could be low in this patient group because of older age as well. Authors mentioned this limitation briefly in the discussion, but I think this is major flaw and authors should explore this further. I suggest that the Mean age of the healthy group should be available as a table as well to compare these groups. This study does not really reflect any new findings as the booster dose is already recommended by CDC and ACIP for anyone 12 years and above and immunocompromised children years which include patient of NSCLC as well.

Since our solicitation of reviews, an updated version of this preprint has been published in the Journal of Clinical Oncology and the link to the published manuscript can be found here.