Immunity, T-Cell Responses in Patients Vaccinated Against SARS-CoV-2 With Low-Dose mRNA-1273

Covid19 Vaccine meds and syringe on white
Investigators conducted a study to assess immune responses among individuals vaccinated against SARS-CoV-2 infection with low-dose mRNA-1273.

Individuals who were vaccinated against SARS-CoV-2 infection with the low-dose Moderna (mRNA-1273) vaccine were found to have durable T-cell responses at 7 months. These findings were published in Science.

This phase 1 study of the 25-mcg mRNA-1273 vaccine trial recruited a total of 35 participants. Between March and April 2020, participants were vaccinated 28 days apart at 2 sites in Seattle and Atlanta. Peripheral blood samples were collected prior to vaccination, 14 days after each vaccine dose, and 7 months after administration of the first vaccine dose.

At month 7, 100% of participants sustained anti-spike and receptor-binding domain (RBD) immunoglobulin G (IgG) antibody responses. SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies were detected among 88% of participants at month 7. All 3 antibodies were correlated (r = 0.89-0.90).

Spike-specific CD4+ T-cell responses were observed and maintained through month 7 among 97% of participants after the first vaccine dose and 100% of those after the second dose. In regard to CD8+ T cells, 34% and 53% of participants had a detectable response after the first and second vaccine dose, respectively. The detection at month 7 was similar to that observed among individuals who had passed a COVID-19 infection.

The investigators found a statistically significant correlation between CD4+ and CD8+ T cells (P <.0001), indicating a multifunctional spike-specific response.

After the first and second dose of vaccine, spike-specific circulating T follicular helper cells were detected among 71% and 75% of participants, respectively, and 94% overall. The investigators noted that the varying presentation of these T follicular helper cells showed a differing kinetic response depending on intracellular cytokines.

After stratification by age by age, participants aged 56 years and older were found to have a 2-fold decrease in spike and RBD IgG antibodies at day 209; however, spike-specific and memory CD4+ and CD8+ T cells did not differ significantly compared with younger participants.

Compared with the 25-mcg mRNA-1273 vaccine, the 100-mcg mRNA-1273 vaccine was observed to illicit a 2-fold increase in anti-spike IgG, anti-RBD IgG, and PSV-neutralizing titers and a 1.4- to 2.0-fold increase in spike-specific CD4+ T-cell responses. In addition, CD8+ T-cell responses were similar between the 25- and 100-mcg vaccine doses.

This study was limited by its small sample size and requires replication in larger trials.

“These findings show substantial immune responses and immune memory to a low-dose mRNA vaccine and indicate biologic relevance of cross-reactive memory T cells,” the investigators concluded.

Disclosure: Some author(s) declared affiliations with industry. Please see the original reference for a full list of disclosures.


Mateus J, Dan JM, Zhange Z, et al. Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells. Science. 2021;eabj9853. doi:10.1126/science.abj9853