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

• Published in: Science (American Association for the Advancement of Science) Vol. 374; no. 6566; p. eabj9853
• Main Authors: Mateus, Jose, Dan, Jennifer M., Zhang, Zeli, Rydyznski Moderbacher, Carolyn, Lammers, Marshall, Goodwin, Benjamin, Sette, Alessandro, Crotty, Shane, Weiskopf, Daniela
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 22.10.2021
• Subjects: 2019-nCoV Vaccine mRNA-1273; Adolescent; Adult; Age; Age differences; Aged; Aged, 80 and over; Antibodies; Antibodies, Viral - blood; Antiviral drugs; Between-subjects design; Binding; Blood; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clinical trials; Clinical Trials, Phase I as Topic; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Cross Reactions; Dosage; Durability; Equivalence; Feedback (Response); Helper cells; Humans; Immunity; Immunization; Immunogenicity, Vaccine; Immunologic Memory; Immunological memory; Immunology; Infections; Interferon; Longitudinal Studies; Lymphocytes; Lymphocytes T; Memory; Memory cells; Middle Aged; mRNA; mRNA vaccines; Neutralizing; Patients; Questions; Respiratory diseases; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Vaccination; Vaccines; Viral diseases; Young Adult; γ-Interferon
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abj9853

Low-dose messenger RNA (mRNA) vaccines potentially allow health providers to administer more doses from a limited vaccine supply and can be less reactogenic. Whether low-dose COVID-19 mRNA vaccines generate immune responses comparable to currently approved doses remains an open question, however. Mateus et al . report the results of a clinical trial comparing patients who received a 25-μg mRNA-1273 (Moderna) COVID-19 vaccine to 100-μg mRNA-1273 COVID-19 vaccinees and severe acute respiratory syndrome coronavirus 2–infected individuals. The low-dose Moderna vaccine generated long-lived T cell immunity that was equivalent between younger and older patients and that could be enhanced by the presence of cross-reactive T cells. Moreover, antibody and T cell responses induced by the low-dose vaccine were comparable to natural infection and about half as strong as those seen with high-dose vaccination. —STS A reduced dose of the Moderna SARS-CoV-2 vaccine induces long-lived T cell and antibody responses comparable to natural infection. 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.