Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Emerging evidence suggests longer intervals between SARS-CoV-2 vaccine doses enhance immune responses.
• The optimal dosing interval for maximizing immunogenicity of COVID-19 vaccines remains unclear.

Purpose of the Study:

• To investigate the association between varying mRNA vaccine dosing intervals and immune responses.
• To determine the optimal interval for achieving maximum immunogenicity after COVID-19 vaccination.

Main Methods:

• Adult paramedics in Canada received two doses of BNT162b2 or mRNA-1273 vaccines.
• Blood samples were collected six months after the first vaccine dose.
• Vaccine dosing intervals were categorized into quartiles: short (≤30 days), moderate, long (39-73 days), and longest (≥74 days).
• Primary outcome: total spike antibody concentrations. Secondary outcomes: spike and RBD IgG antibody concentrations, ACE-2 binding inhibition.

Main Results:

• Longer intervals (long and longest quartiles) were associated with increased total spike antibody concentrations compared to short intervals.
• The longest interval quartile showed higher spike IgG antibodies, while long and longest intervals showed higher RBD IgG antibody concentrations.
• Extended dosing intervals also increased the inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to viral spike proteins.

Conclusions:

• mRNA vaccine dosing intervals exceeding 38 days lead to higher anti-spike antibody levels.
• Longer intervals enhance ACE-2 inhibition, indicating improved neutralization capacity.
• These findings support extended dosing intervals for potentially optimizing COVID-19 vaccine effectiveness.