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Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

ABSTRACT: An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.

SUBMITTER: Boutriau D

PROVIDER: S-EPMC1797715 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

Boutriau Dominique D Poolman Jan J Borrow Ray R Findlow Jamie J Domingo Javier Diez JD Puig-Barbera Joan J Baldó José María JM Planelles Victoria V Jubert Angels A Colomer Julia J Gil Angel A Levie Karin K Kervyn Anne-Diane AD Weynants Vincent V Dominguez Francisco F Barberá Ramon R Sotolongo Franklin F

Clinical and vaccine immunology : CVI 20061025 1

An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 mo ...[more]

PMID: 17065257

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Project description:Key pointsConcomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations.BackgroundBivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086.MethodsHealthy adolescents aged ≥11 to <19 years received bivalent rLP2086 + DTaP/IPV or saline + DTaP/IPV at month 0 and bivalent rLP2086 or saline at months 2 and 6. The primary end point was the proportion of participants in whom prespecified levels of antibodies to DTaP/IPV were achieved 1 month after DTaP/IPV administration. Immune responses to bivalent rLP2086 were measured with serum bactericidal assays using human complement (hSBAs) against 4 MnB test strains expressing fHBP subfamily A or B proteins different from the vaccine antigens.ResultsParticipants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events.ConclusionsImmune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270.

Project description:BackgroundDeclining antimicrobial susceptibility to current gonorrhoea antibiotic treatment and inadequate treatment options have raised the possibility of untreatable gonorrhoea. New prevention approaches, such as vaccination, are needed. Outer membrane vesicle meningococcal serogroup B vaccines might be protective against gonorrhoea. We evaluated the effectiveness of a serogroup B meningococcal outer membrane vesicle vaccine (MenB-4C) against gonorrhoea in individuals aged 16-23 years in two US cities.MethodsWe identified laboratory-confirmed gonorrhoea and chlamydia infections among individuals aged 16-23 years from sexually transmitted infection surveillance records in New York City and Philadelphia from 2016 to 2018. We linked gonorrhoea and chlamydia case records to immunisation registry records to determine MenB-4C vaccination status at infection, defined as complete vaccination (two MenB-4C doses administered 30-180 days apart), partial vaccination (single MenB-4C vaccine dose), or no vaccination (serogroup B meningococcal vaccine naive). Using log-binomial regression with generalised estimating equations to account for correlations between multiple infections per patient, we calculated adjusted prevalence ratios (APR) and 95% CIs to determine if vaccination was protective against gonorrhoea. We used individual-level data for descriptive analyses and infection-level data for regression analyses.FindingsBetween Jan 1, 2016, and Dec 31, 2018, we identified 167 706 infections (18 099 gonococcal infections, 124 876 chlamydial infections, and 24 731 gonococcal and chlamydial co-infections) among 109 737 individuals linked to the immunisation registries. 7692 individuals were vaccinated, of whom 4032 (52·4%) had received one dose, 3596 (46·7%) two doses, and 64 (<1·0%) at least three doses. Compared with no vaccination, complete vaccination series (APR 0·60, 95% CI 0·47-0·77; p<0·0001) and partial vaccination series (0·74, 0·63-0·88; p=0·0012) were protective against gonorrhoea. Complete MenB-4C vaccination series was 40% (95% CI 23-53) effective against gonorrhoea and partial MenB-4C vaccination series was 26% (12-37) effective.InterpretationMenB-4C vaccination was associated with a reduced gonorrhoea prevalence. MenB-4C could offer cross-protection against Neisseria gonorrhoeae. Development of an effective gonococcal vaccine might be feasible with implications for gonorrhoea prevention and control.FundingNone.

Project description:There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.

Project description:Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development. There are a few licensed OMV vaccines mainly for the prevention of meningitis caused by Neisseria meningitidis serogroup B (MenB) and Haemophilus influenzae type b (Hib). There are several candidates in clinical development against other gram-negative organisms from which the OMVs are derived, but also against heterologous targets in which the OMVs are used as carriers (e.g. coronavirus disease 2019 [COVID-19]). The use of OMVs for targets other than those from which they are derived is a major advancement in OMV technology, improving its versatility by being able to deliver protein or polysaccharide antigens. Other advances include the range of genetic modifications that can be made to improve their safety, reduce reactogenicity, and increase immunogenicity and protective efficacy. However, significant challenges remain, such as identification of general tools for high-content surface expression of heterologous proteins on the OMV surface. Here, we outline the progress of OMV vaccines to date, particularly discussing licensed OMV-based vaccines and candidates in clinical development. Recent trends in preclinical research are described, mainly focused on genetic manipulation and chemical conjugation for the use of OMVs as carriers for heterologous protein and polysaccharide antigens. Remaining challenges with the use of OMVs and directions for future research are also discussed.

Dataset Information

Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

Publications

Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

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