Extended synopsis of the study protocol.

<div><p>Background</p><p>Pacific Islanders are underrepresented in vaccine efficacy trials. Few studies describe their immune response to COVID-19 vaccination. Yet, this characterization is crucial to re-enforce vaccination strategies adapted to Pacific Islanders singularities.</p><p>Methods and findings</p><p>We evaluated the humoral immune response of 585 adults, self-declaring as Melanesians, Europeans, Polynesians, or belonging to other communities, to the Pfizer BNT162b2 vaccine. Anti-spike and anti-nucleoprotein IgG levels, and their capacity to neutralize SARS-CoV-2 variants and to mediate antibody-dependent cellular cytotoxicity (ADCC) were assessed across communities at 1 and 3 months post-second dose or 1 and 6 months post-third dose. All sera tested contained anti-spike antibodies and 61.3% contained anti-nucleoprotein antibodies, evidencing mostly a hybrid immunity resulting from vaccination and SARS-CoV-2 infection. At 1-month postimmunization, the 4 ethnic communities exhibited no significant differences in their anti-spike IgG levels (<i>p</i> value = 0.17, in an univariate linear regression model), in their capacity to mediate omicron neutralization (<i>p</i> value = 0.59 and 0.60, in an univariate logistic regression model at 1-month after the second and third dose, respectively) and in their capacity to mediate ADCC (<i>p</i> value = 0.069 in a multivariate linear regression model), regardless of the infection status. Anti-spike IgG levels and functionalities of the hybrid humoral immune response remained equivalent across the 4 ethnic communities during follow-up and at 6 months post-third dose.</p><p>Conclusions</p><p>Our study evidenced Pacific Islander’s robust humoral immune response to Pfizer BNT162b2 vaccine, which is pivotal to re-enforce vaccination deployment in a population at risk for severe COVID-19 (<a href="http://clinicaltrials.gov" target="_blank">clinicaltrials.gov</a>: NCT05135585).</p><p>Trial registration</p><p>This trial has been register in ClinicalTrials.gov (ID: <a href="https://clinicaltrials.gov/ct2/show/NCT05135585" target="_blank">NCT05135585</a>).</p></div>