World Experience in the Use Serogroup B Meningococcal Vaccines (literature review)

Relevance. The success of vaccine prophylaxis of meningococcal infection depends on the composition and properties of vaccine preparations and the strict implementation of recommendations on vaccine prophylaxis tactics by the territorial epidemiological characteristics of meningococcal infection. Despite the high burden of B-meningococcal infection, especially among young children, the design of B-meningococcal vaccines has faced serious difficulties. Aim. The literature review presents the history of the development of B-meningococcal vaccines and provides characteristics of two immunologically effective and safe new generation B-meningococcal vaccine preparations. Conclusion. The licensing of the two new B-meningococcal vaccines presented in the review (Bexsero and Trumenba) was based on immunogenicity and safety. The inclusion of vaccines in national vaccination programs requires careful analysis, including analysis of the antigenic characteristics of circulating strains.

04. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Meningococcal Vaccine-Naive Participants Across a Broad Age Range (2-55 Years) in Japan

Background MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and certain other countries. We evaluated the safety and immunogenicity of MenACYW-TT compared to a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-DT [Menactra®]) in Japanese children, adolescents and adults (2-55 years of age). Methods A phase III modified double-blind, randomized study (NCT04368429) to evaluate the immunogenicity and safety of a single dose of MenACYW-TT versus MenACWY-DT was conducted in 360 participants (ratio 1:1) between ages 2 and 55 years in Japan. Serum bactericidal assays with human complement (hSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0) and 30 days post-vaccination (D30). Safety data were collected up to 30 days post-vaccination. Results Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse as primary endpoint, was demonstrated for MenACYW-TT compared to MenACWY-DT at Day 30 in comparison to baseline: 85.6% vs 65.4% for serogroup A, 96.6% vs 62.6% for serogroup C, 87.4% vs 49.2% for serogroup W, and 97.7% vs 63.5% for serogroup Y. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-DT administration for serogroups C (98.9% vs 81.0%), W (99.4% vs 91.1%) and Y (100 % vs 89.4%) and comparable for serogroup A (96.6% vs 92.7%). The hSBA GMTs were higher following administration of MenACYW-TT for all four serogroups. Immunogenicity results in participants 10 to 17 years of age and ≥ 18 years of age were comparable to those in the whole population (2-55 years). The safety profiles of MenACYW-TT and MenACWY-DT were comparable. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study. Conclusion MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared to that for the licensed MenACWY-DT vaccine when administered as a single dose to meningococcal vaccine-naïve children, adolescents, and adults in Japan. Disclosures Osamu Matsuoka, MD, Sanofi Pasteur (Scientific Research Study Investigator, Research Grant or Support) Mugen Ujiie, MD, Sanofi Pasteur (Scientific Research Study Investigator, Research Grant or Support) Hitoshi Kikuchi, MD, Sanofi Pasteur (Scientific Research Study Investigator)Sanofi Pasteur (Research Grant or Support) Danaya Chansinghakul, MD, Sanofi Pasteur (Employee) Takahiro Inoue, MSc, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Nuchra Sirisuphmitr, MSc, Sanofi Pasteur (Employee) Tomoyuki Hashiguchi, MSc, Sanofi Pasteur (Employee) Betzana Zambrano, MD, Sanofi Pasteur (Employee) Takahiro Nakama, MD, Sanofi Pasteur (Employee) Carina Frago, MD, Sanofi Pasteur (Employee, Shareholder) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder)

Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial

Background HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. Methods We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. Discussion This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. Trial registration ClinicalTrials.gov NCT03675256. Registered on September 18, 2018

Exploring the Ability of Meningococcal Vaccines to Elicit Mucosal Immunity: Insights from Humans and Mice

Neisseria meningitidis causes a devastating invasive disease but is also a normal colonizer of the human nasopharynx. Due to the rapid progression of disease, the best tool to protect individuals against meningococcal infections is immunization. Clinical experience with polysaccharide conjugate vaccines has revealed that an ideal meningococcal vaccine must prevent both invasive disease and nasal colonization, which confers herd immunity. However, not all meningococcal vaccines are equal in their ability to prevent nasal colonization, for unknown reasons. Herein, we describe recent efforts to utilize humanized mouse models to understand the impact of different meningococcal vaccines on nasal colonization. These mice are susceptible to nasal colonization, and they become immune following live nasal infection or immunization with matched capsule-conjugate or protein-based vaccines, replicating findings from human work. We bring together insights regarding meningococcal colonization and immunity from clinical work with findings using humanized mouse models, providing new perspective into the different determinants of mucosal versus systemic immunity. Then, we use this as a framework to help focus future studies toward understanding key mechanistic aspects left unresolved, including the bacterial factors required for colonization and immune evasion, determinants of nasal mucosal protection, and characteristics of an ideal meningococcal vaccine.

Single-dose HPV Vaccination Efficacy Among Adolescent Girls and Young Women in Kenya (the KEN SHE Study): Study Protocol for a Randomized Controlled Trial

Background: HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limits widespread implementation of the current two or three dose HPV vaccine schedule. Methods: We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15-20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to: 1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; 2) assess the memory B cell immune response at months 36 and 37; and 3) estimate cost-effectiveness using the trial results and health economic models. Discussion: This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. Trial registration: NCT03675256