Safety and Immunogenicity Study of Group B Meningococcal Vaccine to Prevent Meningitis.

Phase 1

Completed

Interventions: Biological: 25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine
Biological: 50ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine

Brief Summary: The purpose of this study is to determine if the vaccine called Group B Meningococcal 44/76 MOS NOMV 5D Vaccine is safe and free from side effects and if it will protect people from meningitis.

This study will vaccinate three groups of people. In the first 2 groups, the study will be double-blinded. This means that neither the volunteer or the medical team will know which formulation of the vaccine was administered. The third group of volunteers and the medical team will know that they are receiving the higher dose of the vaccine.

Detailed Description: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis that can kill children and young adults very quickly. Meningococci are divided into distinct sergroups based on their polysaccharide outer capsule, which is the usual target antigen for vaccines. Serogroup A is the main cause of epidemics in Africa and in the United States, sergroups B, C and Y predominate. In the United States, no vaccine is yet available to offer protection against serogroup B which currently accounts for 32% of all meningococcal disease in the United States.

This study serves as a proof of concept for our new NOMV Group B single strain monovalent vaccine model which is obtained from a genetically modified parent. If successful we plan to develop a multivalent Group B vaccine for routine use for military recruits at the beginning of basic training, for college students, particularly those who live in dormitories, and for use by travelers to countries recognized as having hyperendemic disease.

Recruitment & Eligibility

Inclusion Criteria

Healthy military or civilian males or non-pregnant, non-lactating females
Age 18-45
Give informed consent and understand risk and benefit of study
Understands and willing to comply with all protocol procedures and time commitment
FEMALES only: surgically sterilized or received a negative pregnancy test on day of first injection AND agrees to practice adequate birth control, if necessary, for the next 7 months after first vaccination.

Exclusion Criteria

Currently has or has had a history of significant organ/system disease
History of allergy to any vaccine
Allergy to component of vaccine such as aluminum hydroxide
Presence of significant unexplained laboratory abnormality
HIV sero-positive or any other immunosuppressive state
Positive test for HBsAg, or hepatitis C
Ongoing drug abuse/dependence
Received any live vaccine, experimental products or immunosuppressive therapy in the last 28 days or inactivated vaccine in the past 14 days, or received parenteral immunoglobulin or blood products within the past 3 months
Intention to leave study area for an extended period of time during the study
Females: positive urine pregnancy test prior to vaccination

Arm && Interventions

Group	Intervention	Description
1) 25ug Group B Meningococcal 44/76 MOS NOMV 5D w/o adjuvant	25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine	Subjects received 25ug Group B Meningococcal 44/76 MOS NOMV 5D without AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks.
3) 50ug Group B Meningococcal 44/76 MOS NOMV 5D w/o adjuvant	50ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine	Subjects received 50ug Group B Meningococcal 44/76 MOS NOMV 5D without AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks.
2) 25ug Group B Meningococcal 44/76 MOS NOMV 5D with adjuvant	25ug Group B Meningococcal 44/76 MOS NOMV 5D Vaccine	Subjects received 25ug Group B Meningococcal 44/76 MOS NOMV 5D with AI (OH)3 adjuvant intramuscularly at 0, 6, and 24 weeks.

Primary Outcome Measures

Name	Time	Method
Safety: Adverse Event Type Summarized by Dose	7 days after each vaccination	Adverse events summarized by type and dose
Safety: Severity Summary of Solicited and Unsolicited Adverse Events	7 day f/u period after each vaccination	Solicited and unsolicited summary of severity of adverse events (AEs) during the 7 day follow-up period after each vaccination

Secondary Outcome Measures

Name	Time	Method
Weeks to Serconversion	26 weeks	Weeks to seroconversion evaluated by serum bactericidal assay. Immunogenicity was determined by assessing the number of subjects, in each cohort, who seroconverted. Seroconversion was defined as a 4-fold or greater increase in serum bactericidal antibodies against the vaccine strain. The geometric mean bactericidal titer (GMT) for each group was determined prior to vaccination and at 2 weeks after each vaccination. For each group, the GMT ratio relative to baseline and after 1, 2, or 3 vaccinations and the 95% 2-sided confidence interval was determined. A seroconversion of ≥50% of the subjects after 2 or more doses would meet the criteria for further vaccine development.
Percentage of Subjects With 2-fold and 4-fold Increase IgG Antibody Conversion	26 weeks	Percentage of subjects with ELISA 2-fold and 4-fold increase from baseline IgG antibody Conversion