6. Pentavalent Meningococcal (MenABCWY) Vaccine is Safe and Well Tolerated With Immunogenicity Noninferior to Coadministered MenB-FHbp and MenACWY-CRM in a Phase 2 Study of Healthy Adolescents and Young Adults

Abstract

Background Meningococcal serogroups A, B, C, W and Y cause nearly all meningococcal disease globally. Vaccination is complicated by different dosing recommendations for serogroup B (MenB) and quadrivalent (MenACWY) vaccines, which could be solved with a single pentavalent vaccine. This study in adolescents and young adults evaluated a new pentavalent MenABCWY vaccine that combines 2 licensed vaccines, MenB-FHbp (Trumenba®; bivalent rLP2086) and MenACWY-TT (Nimenrix®), into a single vaccine. Methods In this ongoing, randomized, controlled, observer-blinded, multicenter study (NCT03135834), MenB vaccine-naive and MenACWY-naive or -experienced healthy 10–25-year-olds were randomized 1:2 to MenABCWY (Month 0,6) or MenB-FHbp (Month 0,6) and MenACWY-CRM (Month 0). Immune responses were measured by serum bactericidal activity assays with human complement (hSBA) against serogroup A, C, W and Y strains and 4 diverse, vaccine-heterologous MenB strains. Endpoints included percentages of subjects achieving ≥ 4-fold rises in titers from baseline. Noninferiority of immune responses was assessed at the 10% margin (95% CI lower limit > −10%). Safety was assessed. Results Following dose 2, high percentages of MenABCWY (n=543) and MenB-FHbp (n=1057) recipients achieved ≥ 4-fold rises against each of the 4 MenB strains (75.8−94.7% vs 67.4−95.0%) and titers reaching at least the lower limit of quantification against all 4 strains combined (79.9% vs 74.3%; Figure 1A). MenABCWY was noninferior to MenB-FHbp for all 5 endpoints. MenABCWY was also noninferior to a single MenACWY-CRM dose with 75.5−96.9% and 93.0−97.4% of MenABCWY recipients after dose 1 or 2, respectively, achieving ≥ 4-fold rises against serogroup A, C, W and Y depending on prior MenACWY experience (Figure 1B). Local reactions and systemic events after MenABCWY or MenB-FHbp were similarly frequent, mostly mild/moderate in severity (Figure 2), and unaffected by MenACWY experience. Figure 1. Immune Responses as Measured in hSBA to (A) MenB Test Strains at 1 Month After Dose 2 and (B) MenA, MenC, MenW, and MenY Test Strains at 1 Month After Doses 1 and 2 Figure 2. (A) Local Reactions and (B) Systemic Events Reported Within 7 Days After Any Dose Conclusion MenABCWY 4-fold immune responses from baseline were robust and noninferior to MenB-FHbp and MenACWY-CRM administered separately. Vaccination was safe and well tolerated. The favorable benefit-risk profile supports further MenABCWY development as a simplified alternative to current meningococcal vaccination practices. Funded by Pfizer. Disclosures James Peterson, MD, Pfizer (Scientific Research Study Investigator) Daniel Drazan, MD, Pfizer (Scientific Research Study Investigator) Hanna Czajka, MD, PhD, Pfizer (Scientific Research Study Investigator) Jason Maguire, MD, Pfizer (Employee, Shareholder) Jean-Louis Pregaldien, MS, Pfizer (Employee, Shareholder) Ilkka Seppa, MD, Pfizer (Scientific Research Study Investigator) Roger Maansson, MS, Pfizer (Employee, Shareholder) Robert O’Neill, PhD, Pfizer (Employee, Shareholder) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Paul Balmer, PhD, Pfizer Inc (Employee, Shareholder) Johannes Beeslaar, MD, Pfizer (Employee, Shareholder) John L. Perez, MD, MA, Pfizer Inc (Employee, Shareholder)

Managing infectious challenges in the age of molecular‐targeted therapies for adult hematological malignancies

“…Booster doses of MenACWY and Men B should be administered according to the recommended schedules 108 . More recently, the FDA has approved meningococcal groups A, B, C, W, and Y vaccine (Penbraya), the first and only pentavalent vaccine 109 . Nonetheless, physicians should remain vigilant for breakthrough meningococcal infections despite vaccination 110,111 .…”

“…108 More recently, the FDA has approved meningococcal groups A, B, C, W, and Y vaccine (Penbraya), the first and only pentavalent vaccine. 109 Nonetheless, physicians should remain vigilant for breakthrough meningococcal infections despite vaccination. 110,111 As vaccination efficacy can be impaired in patients on other concomitant immunosuppressive agents, chemoprophylaxis with ciprofloxacin 500 mg daily or penicillin V 250 mg every 12 h should be considered.…”

Meningococcal Disease and Immunization Activities in Hajj and Umrah Pilgrimage: a review

“…Novel pentavalent vaccines are in clinical development. These include a pentavalent vaccine targeting MenX (i.e., MenACWY and X), principally to address MenW emergence in sub-Saharan Africa [114,115], and vaccines combining 4CMenB or MenB-FHbp vaccine components with MenACWY elements as MenABCWY formulations [116][117][118]. These pentavalent vaccines are in the latter stages of clinical development and could be available within the next 5 years.…”

Rationale for the Development of a Pentavalent Meningococcal Vaccine: A US-Focused Review

“…The MenABCWY vaccine is being investigated in an ongoing phase 2/3 study in healthy adolescents and young adults 10-25 years of age, including both MenACWY vaccine-naive and -experienced subjects (NCT03135834) [57]. After administration of a 2-dose schedule given at months 0 and 6 (control subjects received MenB-FHbp at months 0 and 6 and MenACWY-CRM [Menveo Ò ; GSK Vaccines, Sovicille, Italy] at month 0), immune responses to MenABCWY were robust and noninferior to MenB-FHbp and MenACWY-CRM at 1 month after dose 2, regardless of prior MenACWY vaccine exposure [57]. MenABCWY was also well tolerated with an acceptable safety profile [57].…”

“…After administration of a 2-dose schedule given at months 0 and 6 (control subjects received MenB-FHbp at months 0 and 6 and MenACWY-CRM [Menveo Ò ; GSK Vaccines, Sovicille, Italy] at month 0), immune responses to MenABCWY were robust and noninferior to MenB-FHbp and MenACWY-CRM at 1 month after dose 2, regardless of prior MenACWY vaccine exposure [57]. MenABCWY was also well tolerated with an acceptable safety profile [57]. Other ongoing clinical studies of the MenABCWY vaccine include phase 2 studies in healthy infants (NCT04645966) and adolescents (NCT04440176), and a phase 3 study in adolescents and young adults (NCT04440163; Table 3).…”