Standard dosing intervals for BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines are 21 and 28 days, respectively. 1 Data suggest improved effectiveness of ChAdOx1 adenoviral 2 and other nonreplicating vaccines 3 with increased dosing intervals, but little data exist for mRNA vaccines. This study investigated the immunogenicity of extended mRNA vaccine dosing intervals.

Health jurisdictions have seen a near-disappearance of Respiratory Syncytial Virus (RSV) during the first year of the COVID-19 pandemic. Over a corresponding period, we report a reduction in RSV antibody levels and neutralization in women and infants one year into the COVID-19 pandemic (February – June 2021) compared to earlier in the pandemic (May – June 2020), in British Columbia (BC), Canada. This supports that humoral immunity against RSV is relatively short-lived and its establishment in infants requires repeated viral exposure. Waned immunity in young children may explain the inter-seasonal resurgence of RSV cases in BC as seen also in other countries.

Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear.

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The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant.

ObjectiveEmerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear.MethodsThis study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples 6 months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as “short” (first quartile), “moderate” (second quartile), “long” (third quartile), and “longest” interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included: spike and RBD IgG antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations.ResultsA total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to “short interval” (≤30 days), higher dosing interval quartiles (moderate: 31-38 days; long: 39-73 days and longest: ≥74 days) were all associated with increased Elescys spike total antibody concentration. Compared to the short interval, “long” and “longest” interval quartiles were associated with higher spike and RBD IgG antibody concentrations. Similarly, increasing dosing intervals increased inhibition of ACE-2 binding to viral spike protein, regardless of the vaccine type.ConclusionIncreased mRNA vaccine dosing intervals longer than 30 days result in higher levels of circulating antibodies and viral neutralization when assessed at 6 months.