Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Vaccine administration site is often disregarded, yet may influence immune responses.
• Understanding factors affecting vaccine efficacy is crucial for public health.

Purpose of the Study:

• To assess if the vaccination arm site impacts serological responses to COVID-19 vaccine boosters.
• To evaluate the long-term effects of contralateral vs. ipsilateral boosting on antibody levels and neutralization.

Main Methods:

• Serological responses were measured in baseline seronegative adults receiving COVID-19 vaccine boosters.
• Participants received boosters in either the ipsilateral or contralateral arm relative to initial vaccination.
• Antibody titers (spike-specific Ig, RBD-specific IgG, nucleocapsid-specific IgG, and neutralizing antibodies) were measured at multiple time points post-boosting.

Main Results:

• Contralateral boosting was associated with higher spike-specific Ig and RBD-specific IgG, with effects increasing up to 14 months.
• Matched pairs showed significantly higher binding and neutralizing antibody titers with contralateral boosting at later time points (W3 and W4).
• Neutralizing antibody titers against SARS-CoV-2 strains (D614G and Omicron) were substantially higher with contralateral boosting.

Conclusions:

• Contralateral boosting with the BNT162b2 mRNA COVID-19 vaccine significantly increases antibody magnitude and breadth in previously unexposed adults.
• The observed increase in antibody response with contralateral boosting persists beyond 3 weeks post-vaccination.
• Arm selection for subsequent vaccine doses may be a relevant consideration for optimizing immune responses in multidose regimens.