Catherine A. Cosgrove

Background: Influenza A viruses pose a persistent pandemic threat. We report safety, reactogenicity, and immunogenicity findings for mRNA-1018 pandemic influenza vaccine candidates from a phase 1/2 study in healthy adults. Methods: In part A, participants were randomized to receive 1 of 4 mRNA-1018 candidates at 1 of 3 dose levels across 2 influenza A groups: (1) H5N8/H5-only or (2) H7N9/H7-only. Part B participants were randomized to receive H5-only-CG. The primary objectives were to evaluate the safety and reactogenicity. The secondary objectives included evaluation of humoral immunogenicity through day 205 by hemagglutination inhibition (HAI), neuraminidase inhibition, and microneutralization assays. Results: Parts A and B comprised 1195 and 304 dosed participants, respectively. Overall, solicited local adverse reactions (ARs) within 7 days of vaccination occurred in 76.8% of participants across vaccine candidates and dose levels, most commonly injection-site pain. Solicited systemic ARs were reported in 62.8% of participants, most frequently fatigue and headache. Postvaccination immune responses, assessed absolutely, by HAI titers and dynamically, by seroconversion rates, tended to increase with vaccine dose. H5-based candidates induced stronger strain-specific HAI. Conclusions: Vaccine candidates were sufficiently well tolerated and immunogenic. Further development of mRNA pandemic influenza vaccines is warranted. Clinical Trials Registration. NCT05972174

Individuals with immunocompromising conditions (e.g. asplenia, complement deficiency, HIV infection) or with high exposure to Neisseria meningitidis (e.g. laboratory workers, those in outbreak settings) have an increased risk of meningococcal disease. Immunization with meningococcal serogroups ACWY (MenACWY) and serogroup B (MenB) vaccines is recommended for high-risk groups in many countries, although definitions of high-risk vary. There are not yet clinical data for the pentavalent meningococcal serogroups ABCWY (MenABCWY) vaccines in high-risk populations. This review examines studies conducted in high-risk groups with the component vaccines of GSK's MenABCWY vaccine, the 4-component MenB vaccine (4CMenB) and quadrivalent MenACWY CRM₁₉₇-glycoconjugate vaccine (MenACWY-CRM). These component vaccines have been licensed for more than 10 years and are recommended in groups categorized as high risk. The component vaccines of GSK's MenABCWY vaccine, 4CMenB and MenACWY-CRM, have demonstrated immunogenicity and safety in high-risk groups, including with concomitant or sequential vaccine administration. As expected, immunogenicity was reduced in patients with complement deficiencies, particularly those receiving eculizumab. Further data are required on meningococcal vaccination in high-risk groups for the future refinement of national and regional recommendations and to support proactive approaches to improve vaccine uptake in high-risk groups.