Researchers studying Moderna's SARS-CoV-2 mRNA-1273 vaccine report that its safety profile and immune response in older people is comparable to that in the younger population they tested earlier, according to phase 1 trial results published yesterday in the New England Journal of Medicine (NEJM).
The messenger RNA vaccine is one of only a few COVID-19 vaccines being studied specifically in older patients, despite their vulnerability during the pandemic.
While the original study pool for the mRNA-1273 vaccine was for adults ages 18 to 55, the researchers expanded the study to include adults ages 56 to 70 and 71 and older, with 20 participants in each age-group. The vaccine is designed to trigger a protective immune response by introducing RNA from the SARS-CoV-2 spike protein (S-2P) into the body.
Higher dosage tied to stronger response
Half (10) of the participants in each age-group received two 25-microgram (μg) doses of the candidate vaccine 27 days apart, and half (10) received two 100-μg doses.
Day 57 results for those who received 25-μg doses showed an anti-S-2P geometric mean titer (GMT) of 323,945 for those 56 to 70 years of age and a GMT of 1,128,391 for those 71 years or older. For those who received 100-μg doses, the GMT was 1,183,066 and 3,638,522, respectively.
All of these were above the GMT of the study's donated convalescent serum, which was 138,901. The vaccine also seemed to evoke a strong CD4 cytokine response with type 1 helper T cells.
Adverse effects were generally mild or moderate and most commonly included fatigue, chills, headache, myalgia and pain at the injection site. All but two instance of moderate systemic adverse effects happened after the second injection, and the researchers reported only two cases of severe systemic effects, also after the second injection. One was fever in the 56-to-70-year-old 25-μg dose subgroup, and the other was fatigue in the 71-and-older 100-μg subgroup.
The authors, from a number of universities across the United States, write, "Important limitations of this study include the small numbers of participants and the limited ethnic diversity. In addition, at the time of this interim report, the long-term durability of immunogenicity could not be assessed, although the magnitude of antibody, cellular, and memory responses will be followed for 12 months after the second vaccination."
The study was partially funded by the National Institutes of Health.
Last month Pfizer published phase 1 data involving adults aged 65 to 85 for its candidate COVID vaccine, and last week Johnson & Johnson posted data on phase 1/2a trials that included 15 people 65 and older. As opposed to findings in the NEJM study, those data were not published in a peer-reviewed journal.
More age-inclusive studies needed
While this is one of the few studies that has focused on older populations, a preliminary literature review of COVID treatment and vaccine trials suggests that more are needed.
In a study published this week in JAMA Internal Medicine, US researchers not involved in the NEJM study surveyed the 847 trials listed on clinictrials.gov and concluded that older adults at high risk have been excluded from more than 50% of COVID-19 clinic trials and 100% of vaccine trials thus far.
The authors looked at direct age cut-offs in study populations—which affected 195 (23%) of the trials—and indirect exclusions that could have a greater impact on older adults, the most cited being compliance and consent concerns, affecting 213 (25%) of the trials. Other common exclusions included broad nonspecified exclusions, specific comorbidities, and technology requirements. (Trials could have more than one exclusion.)
The authors caution that, without more inclusion of older adults, any potential COVID-19 vaccine's effectiveness, use, and adverse effects may not be fully realized or understood.
"Some have argued that only vaccination of younger populations is needed to achieve herd immunity (67% level of immunity), and therefore, vaccination of older adults is not essential," the authors write. "However, the high level of immunity required, coupled with the fact that many settings (eg, nursing homes) are comprised nearly exclusively of older adults, highlights the imperative for their inclusion in COVID-19 vaccine trials."