Enhanced Efficacy of Two-Dose Vaccinations with Arm Alternation

Fresh findings unveil a potential four-fold surge in immune response when individuals switch arms for each dose in multi-dose vaccinations.

A laboratory investigation spearheaded by Oregon Health & Science University (OHSU) researchers scrutinized the antibody response in 947 individuals receiving two-dose COVID-19 vaccinations during the early pandemic phase. This cohort comprised OHSU staff who volunteered for research while undergoing SARS-CoV-2 immunization, randomized to receive their second dose either in the same arm or the opposite one.

Published as a preprint in The Journal of Clinical Investigation, the study challenges the historical belief that arm selection bears no significance.

Analysis of serum samples obtained post-vaccination revealed a marked escalation in both the intensity and breadth of antibody response among those receiving “contralateral” shots—i.e., injections in each arm—compared to those who did not. This heightened immunity manifested three weeks post-second dose and endured beyond 13 months, exhibiting enhanced defense against both the original SARS-CoV-2 strain and the subsequent omicron variant.

While the exact mechanism remains speculative, researchers postulate that administering shots in each arm triggers distinct immune responses in the respective lymph nodes.

OHSU seized the opportunity to explore this inquiry through a series of laboratory investigations involving willing employees, yielding a string of published studies on immune response durability, breadth, and potency post-vaccination and during breakthrough infections.

Following vaccine availability in late 2020, participants pondered whether alternating arms could impact the two-dose regimen’s efficacy.

Among those consenting to arm alternation, researchers paired 54 individuals based on age, gender, and relevant vaccination-to-exposure intervals—half receiving both doses in one arm and the other half alternating. Two weeks post-second dose, no notable difference in immune response was observed. However, by the third week, blood samples exhibited significantly elevated levels of antibodies capable of binding and neutralizing SARS-CoV-2. This elevation progressively intensified over four weeks, reaching up to a four-fold surge against the omicron variant.

Given the widespread exposure to SARS-CoV-2 through vaccination or infection, the study’s focus on COVID-19 vaccines is notable. Nonetheless, researchers anticipate similar immune response enhancements in other multi-dose vaccinations, advocating for further investigation—especially concerning pediatric populations.