Immunogenicity and Safety Testing of a Group B Intranasal Meningococcal Native Outer Membrane Vesicle Vaccine

Abstract

The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Meningitis and septicemia from Neisseria meningitidis continue to represent a major worldwide threat. In the United States 2,500 to 3,000 cases of meningococcal disease occur each year. This is associated with significant morbidity, with up to 19% of survivors being left with neurologic sequelae (3). Most of the outbreaks in the United States are caused by serogroups B, C, and Y, with the predominance of cases occurring in young adults and infants. Multistate surveillance conducted between 1992 and 1996 reported 35% serogroup C cases, 32% B cases, and 26% Y cases (12). Serogroup C is responsible for the majority of cases in the adolescent population, whereas cases in infants less than 1 year old are more often due to group B.Presently licensed vaccines are available to immunize against serogroups A, C, Y, and W-135. Unfortunately, a licensed vaccine is not available against group B meningococci. The difficulties in developing a group B vaccine have included the lack of immunogenicity of the purified capsular polysaccharide (10,17). Attempts at improving the immunogenicity have included noncovalent complexing and covalent conjugating of the polysaccharide to proteins. Zollinger et al. demonstrated transient increases in specific immunoglobulin M (IgM) antibodies after noncovalent complexing, but these antibodies were not bactericidal with human complement (18). The covalent conjugate vaccines using unmodified B capsular polysaccharide did not yield any better results and were basically not protective or immunogenic in animals. Chemically modified B polysaccharide conjugated to recombinant meningococcal PorB is immunogenic in animals and induces a relatively high-quality antibody response, including IgG antibodies that are bactericidal with homologous complement, but safety and immunogenicity in humans have not been demonstrated (6).The approach shifted to developing lipopolysaccharide (LPS)-depleted ou...

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

“…Although a number of safety concerns have been related to their use as adjuvants, particularly the amount of LPS contained within the vesicles, it is clear that both NOMV and DOMV are safe when given intranasally to adults [34,35]. This study could therefore represent a first step towards the development of a rationally designed dual vaccine against both meningitis and RSV, whereby advantage is taken of the adjuvant properties of one antigen to modulate the immune response to the other.…”

“…Virus titrations were carried out as described [5]. NOMV containing approximately 25-50% LPS (relative to protein by weight) and DOMV with 5-8% LPS [35] were produced from mutant 44/76 Mu-4 of Neisseria meningitidis as described [31,38]. Both OMV preparations were tested for sterility and standardised according to their protein content.…”

Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer

“…Although this study confirmed that whole cell antigen induced an ideal antitumor immune response, it contained the normal cellular components, which make immune tolerance and autoimmunity possible. Additionally, the tumor antigen content cannot be easily controlled, which causes difficulty in the application of DC-sensitized antigen (27)(28)(29).…”

Immunization to Protect the U.S. Armed Forces: Heritage, Current Practice, Prospects

“…These threats included natural, endemic diseases, and microbes that could be deployed as bioweapons. (130,178) Such vaccines have been studied to prevent Argentine hemorrhagic fever (AHF, Junín virus), (152,254,255) botulism, (256) Chikungunya, (152,257,258) dengue fever, (254,259) eastern equine encephalitis (EEE), (260) Ebola fever, (152,254,261,262) Escherichia coli, (33,263) hepatitis E, (264) HIV disease, (265)(266)(267)(268) Lassa fever, (152,254,261), malaria, (269-272) Mycoplasma pneumoniae, (273) Neisseria meningitidis serogroup B, (274,275) Q fever, (180,276,277) Rift Valley fever, (152,254,(278)(279)(280)(281)(282) shigellosis, (33,283) tularemia, (180,227,(284)(285)(286)(287) Venezuelan equine encephalitis (VEE), …”