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Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells.

ABSTRACT: Vaccine-specific CD4⁺ T cell, CD8⁺ T cell, binding antibody, and neutralizing antibody responses to the 25-μg Moderna messenger RNA (mRNA)–1273 vaccine were examined over the course of 7 months after immunization, including in multiple age groups, with a particular interest in assessing whether preexisting cross-reactive T cell memory affects vaccine-generated immunity. Vaccine-generated spike-specific memory CD4⁺ T cells 6 months after the second dose of the vaccine were comparable in quantity and quality to COVID-19 cases, including the presence of T follicular helper cells and interferon-γ–expressing cells. Spike-specific CD8⁺ T cells were generated in 88% of subjects, with equivalent memory at 6 months post-boost compared with COVID-19 cases. Lastly, subjects with preexisting cross-reactive CD4⁺ T cell memory exhibited stronger CD4⁺ T cell and antibody responses to the vaccine, demonstrating the biological relevance of severe acute respiratory syndrome coronavirus 2–cross-reactive CD4⁺ T cells.

SUBMITTER: Mateus J

PROVIDER: S-EPMC8542617 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells.

Mateus Jose J Dan Jennifer M JM Zhang Zeli Z Rydyznski Moderbacher Carolyn C Lammers Marshall M Goodwin Benjamin B Sette Alessandro A Crotty Shane S Weiskopf Daniela D

Science (New York, N.Y.) 20211022 6566

Vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25-μg Moderna messenger RNA (mRNA)–1273 vaccine were examined over the course of 7 months after immunization, including in multiple age groups, with a particular interest in assessing whether preexisting cross-reactive T cell memory affects vaccine-generated immunity. Vaccine-generated spike-specific memory CD4+ T cells 6 months after the second dose of the vac ...[more]

PMID: 34519540

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Project description:BackgroundCompared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 μg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days.MethodsThe mRNA-1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals.ResultsAmong 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%).ConclusionDose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.

Dataset Information

Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells.

Publications

Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells.

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