Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 20;40(33):3808-3816.
doi: 10.1200/JCO.21.02986. Epub 2022 Jun 27.

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

Rajesh M Valanparambil  1   2 , Jennifer Carlisle  3 , Susanne L Linderman  1   2 , Akil Akthar  1   2 , Ralph Linwood Millett  3 , Lilin Lai  1   4   5 , Andres Chang  1   2   3   6 , Ashley A McCook-Veal  7 , Jeffrey Switchenko  8 , Tahseen H Nasti  1   2 , Manpreet Saini  1   2   9 , Andreas Wieland  1   2   10   11 , Kelly E Manning  1   4   5 , Madison Ellis  1   4   5 , Kathryn M Moore  1   4   5 , Stephanie L Foster  1   4   5 , Katharine Floyd  1   4   5 , Meredith E Davis-Gardner  1   4   5 , Venkata-Viswanadh Edara  1   4   5 , Mit Patel  1   4   5 , Conor Steur  3   6 , Ajay K Nooka  3   6 , Felicia Green  3 , Margaret A Johns  3 , Fiona O'Brein  3 , Uma Shanmugasundaram  3   6 , Veronika I Zarnitsyna  1   12 , Hasan Ahmed  1   12 , Lindsay E Nyhoff  1   13 , Grace Mantus  1   13 , Michael Garett  2   14 , Srilatha Edupuganti  2   14 , Madhusmita Behra  3 , Rustom Antia  1   12 , Jens Wrammert  1   13 , Mehul S Suthar  1   4   5 , Madhav V Dhodapkar  3   6 , Suresh Ramalingam  3 , Rafi Ahmed  1   2
Affiliations

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

Rajesh M Valanparambil et al. J Clin Oncol. .

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.

PubMed Disclaimer

Conflict of interest statement

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

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
Antibody response to SARS-CoV-2 mRNA vaccine in patients with NSCLC. Binding antibody titers to spike, RBD, and NTD antigens were measured by MSD assay 1 month after the two-dose primary vaccination. Spike-, RBD-, and NTD-specific antibody titers in plasma from healthy vaccinees, patients with NSCLC, and patients with NSCLC with prior exposure to SARS-CoV-2 infection are shown for (A-C) IgG, (D-F) IgA, and (G-I) IgM, respectively. Prepandemic plasma samples from healthy individuals were used to set the detection limit for SARS-CoV-2–specific antibody titers. The figures show the mean and SEM. *P ≤ .05, **P ≤ .01, ***P ≤ .001, and ****P ≤ .0001. IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; MSD, Meso Scale Discovery; ns, not significant; NSCLC, non–small-cell lung cancer; NTD, N-terminal domain; RBD, receptor-binding domain.
FIG 2.
FIG 2.
Live virus–neutralizing antibody response to SARS-CoV-2 mRNA vaccine in patients with NSCLC. Neutralizing antibody titers to WT (614D) virus were evaluated 1 month after the two-dose primary vaccination by FRNT assay. (A) Live virus neutralization of WT (614D) virus by sera from patients with NSCLC compared with the samples from healthy vaccinees. (B) Correlation of spike-specific IgG titer and FRNT50 titer (neutralization titer). (C) Correlation between RBD-specific IgG titer and FRNT50 titer (neutralization titer). Simple linear regression analysis was performed to do correlation analysis, and P values were obtained from the Pearson r correlation method. The figure shows the mean and SEM. ****P ≤ .0001. FRNT, Focus Reduction Neutralization Test; IgG, immunoglobulin G; NSCLC, non–small-cell lung cancer; RBD, receptor-binding domain; WT, wild type.
FIG 3.
FIG 3.
Influence of age and treatment regimens on the antibody response to mRNA vaccination in patients with NSCLC. (A) Patients with NSCLC were divided into four age groups (50-60, 60-70, 70-80, and 80-90 years) and their binding antispike IgG titers were determined. (B) Effect of different cancer therapies (no therapy, PD-1 therapy, and PD-1 with chemotherapy, chemotherapy, and targeted therapy) on the spike-specific IgG titers in response to the mRNA vaccines. The figure shows the mean and SEM. **P ≤ .01. IgG, immunoglobulin G; ns, not significant; NSCLC, non–small-cell lung cancer; PD-1, programmed death-1.
FIG 4.
FIG 4.
Neutralizing antibody response to Delta, Beta, and Omicron SARS-CoV-2 variants in patients with NSCLC after mRNA vaccination. Live virus neutralization of WT (614D), B.1.617.2 (Delta), B.1.351 (Beta), and B.1.1.529 (Omicron) virus by patients with NSCLC 30 days after two-dose primary mRNA vaccination. The figure shows the mean and SEM. ***P ≤ .001, ****P ≤ .0001. FRNT, Focus Reduction Neutralization Test; NSCLC, non–small-cell lung cancer; WT, wild type.
FIG 5.
FIG 5.
(A) Binding and (B) neutralizing antibody titer responses to SARS-CoV-2 wild-type and Omicron variants in patients with NSCLC before booster vaccination and 5-60 days and 60-110 days after booster vaccination. The figure shows the mean and SEM. **P ≤ .01, ***P ≤ .001, and ****P ≤ .0001. FRNT, Focus Reduction Neutralization Test; IgG, immunoglobulin G; NSCLC, non–small-cell lung cancer; WT, wild type.
FIG A1.
FIG A1.
(A-C) Spike versus RBD and (D-F) spike versus NTD. IgG, immunoglobulin G; NTD, N-terminal domain; RBD, receptor-binding domain.
FIG A2.
FIG A2.
Age range of the healthy cohort. IgG, immunoglobulin G; ns, not significant.
FIG A3.
FIG A3.
(A and C) Spike and (B and D) RBD. The figures show the mean and SEM. ***P < .001, ****P < .0001. IgG, immunoglobulin G; ns, not significant; RBD, receptor-binding domain.
FIG A4.
FIG A4.
(A) Healthy vaccinees and (B) patients with NSCLC. The figures show the mean and SEM. ****P < .0001. IgG, immunoglobulin G; ns, not significant; NSCLC, non–small-cell lung cancer.
FIG A5.
FIG A5.
(A) Spike specific IgG response to SARS-CoV-2 variants, (B) healthy vaccinees, and (C) patients with NSCLC. The figures show the mean and SEM. **P < .01, ****P < .0001. IgG, immunoglobulin G; NSCLC, non–small-cell lung cancer; WT, wild type.
See this image and copyright information in PMC

Update of

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Carvalho T, Krammer F, Iwasaki A: The first 12 months of COVID-19: A timeline of immunological insights. Nat Rev Immunol 21:245-256, 2021 - PMC - PubMed
    1. Hu B, Guo H, Zhou P, et al. : Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 19:141-154, 2021 - PMC - PubMed
    1. Polack FP, Thomas SJ, Kitchin N, et al. : Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 383:2603-2615, 2020 - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. : Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 384:403-416, 2020 - PMC - PubMed
    1. Flemming A: Omicron, the great escape artist. Nat Rev Immunol 22:75-75, 2022 - PMC - PubMed

Publication types

Supplementary concepts