Hybrid humoral immune response of Pacific Islanders to BNT162b2 vaccination and Delta/Omicron infection: a cohort study

Background 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. Methods We evaluated the humoral immune response of 585 adults self-declaring as Melanesians, Europeans, Polynesians or belonging to other communities to Pfizer BNT162b2 vaccine. Anti-Spike and anti-Nucleoprotein IgG levels, capacity to neutralize SARS-CoV-2 variants and capacity to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC) were assessed across communities at one and three months post-second dose or one and six months post-third dose. Results 61.3% of the sera tested contained anti-Nucleoprotein antibodies, evidencing mostly a hybrid immunity resulting from vaccination and SARS-CoV-2 infection. Anti-Spike IgG levels and capacity to mediate Omicron neutralization and ADCC were equivalent across the four ethnic communities at one-month post-immunization, during follow-up and at six months post-third dose, regardless of the infection status. Obese individuals (BMI>30 kg/m²) had significantly higher anti-Spike IgG levels at one-month post-immunization (+0.26 (0.04; 0.48) AU in LuLISA assay, p value = 0.017). Odds of Omicron neutralization at six months after the third dose decreased significantly in the 40-64 years and ≥65 years groups (OR (95% CI) 0.48 (0.24-0.90) and 0.29 (0.14-0.58) respectively, p -value = 0.003). Conclusions 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 (clinicaltrials.gov: [NCT05135585][1]). summary Ethnicity has little impact on Pacific Islanders’ hybrid humoral immune response to BNT162b2 vaccination and SARS-CoV-2 infection. Anti-Spike IgG levels, capacity to neutralize Omicron variants and capacity to mediate Antibody-Dependent Cellular Cytotoxicity are equivalent across Pacific communities following BNT162b2 vaccination. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This study was recorded on clinicaltrials.gov (ID: [NCT05135585][1]). ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the “Comité de Protection des Personnes Ile-de-France III” (n° ID-RCB 2021-A01949-32, CPP n° 4003-I, November 9th 2021, Am8898-1-4003 January 17th, 2022, Am9503-2-4003 April, 4th 2022 and Am9508-3-4003 June 21st, 2022) and by the Consultative Ethics Committee of New Caledonia. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Pseudonymized data underlying the results presented in this study are available from the corresponding author, Catherine Inizan (cinizan@pasteur.nc). Requests for reagents and resources should be directed to and will be fulfilled by the corresponding author, Catherine Inizan (cinizan@pasteur.nc). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05135585&atom=%2Fmedrxiv%2Fearly%2F2024%2F04%2F10%2F2024.04.09.24305559.atom