Safety and immunogenicity testing of an intranasal group B meningococcal native outer membrane vesicle vaccine in healthy volunteers

Drabick, Joseph J.; Brandt, Brenda L.; Morán, Elizabeth; Saunders, Nancy B.; Shoemaker, David R.; Zollinger, Wendell D.

doi:10.1016/s0264-410x(99)00216-9

Cited by 65 publications

(50 citation statements)

References 24 publications

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“…Antigens and mitogen in triplicates, together with PBMC (100,000 cells/well) suspended in RPMI 1640 with glutamine (BioWhittaker, Verviers, Belgium) containing 15% human serum, 1% penicillin, and 1% streptomycin, were plated in flat bottom 96 well microtiter plates (Costar, Cambridge, Mass., USA) in final volumes of 200 µl/well. After 6 days of incubation in 5% CO 2 and 5% humidity at 37˚C, the cells were pulsed with 3 Granzyme B Elispot assay. Optimal conditions for antigen-specific prestimulation of PBMC with live influenza virus were used as previously described 15,16 before quantification of granzyme B producing cells in an Elispot assay.…”

Section: Methodsmentioning

confidence: 99%

“…1 In addition to the ease of administration, such vaccines might have the advantage of inducing systemic immune responses of high quality. 2,3 Even though a live influenza-vaccine for intranasal administration has recently been licensed in the USA, there is reason to continue the search for optional non-living mucosal vaccines. 4 It is generally believed that adjuvants are needed for vaccines to be effective when deposited onto mucosal surfaces.…”

Section: Introductionmentioning

confidence: 99%

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A Non-Living Nasal Influenza Vaccine Can Induce Major Humoral and Cellular Immune Responses in Humans without the Need for Adjuvants

Samdal¹,

Bakke²,

Oftung³

et al. 2005

Human Vaccines

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Twenty-eight healthy adult volunteers were immunized intranasally with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1), either in saline or mixed with formaldehyde-inactivated Bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with mucoadhesive properties. After four doses, all groups of vaccinees developed significant IgG-and IgA-antibody responses, measured by ELISA, in respectively serum and nasal secretions. None of the volunteers had demonstrable hemagglutination inhibition (HAI) antibodies in serum before being immunized, whereas more than 80% of them reached HAI titers > 40, considered protective, after immunizations. In addition, cellular immune responses, measured as significant increases in CD4 + T-cell proliferation and granzyme B-producing cytotoxic T-cells, were detected against the vaccine strain as well as against heterologous virus strains (H3N2). However, no additive effect on these responses could be demonstrated with use of B. pertussis or the thixotropic substance in the present vaccines. It appeared, actually, that the mucoadhesive vehicle containing the thixotropic substance was less efficient than were the two other formulations. An influenza vaccine made as a simple particulate formulation of inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an attractive alternative to currently available vaccines.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Non-Living Nasal Influenza Vaccine Can Induce Major Humoral and Cellular Immune Responses in Humans without the Need for Adjuvants

Samdal¹,

Bakke²,

Oftung³

et al. 2005

Human Vaccines

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“…Additionally, such formulations were administered intranasally in order to prevent pyrogenic reactions while mimicking nasopharyngeal colonization by wild-type strains. Drabick et al demonstrated the successful induction of bactericidal antibodies against PorA and L3,7,9 LPS in humans by using an intranasal NOMV vaccine (5). The latter trial used two different doses of vaccine all delivered intranasally.…”

mentioning

confidence: 99%

“…Both lots of vaccine were previously tested intranasally with animals without any pyrogenic effects, and lot no. 0123 was previously studied with 32 healthy volunteers without any significant side effects or febrile reactions (5). All lots passed sterility testing.…”

mentioning

confidence: 99%

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

et al. 2002

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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...

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“…Nevertheless, research on potential antigens created from native outer membrane vesicles (NOMV) and detoxified lipooligosaccharides (dLOS) continues. A series of candidates have been evaluated in humans [56][57][58][59].…”

Section: Meningococcal Vaccinesmentioning

confidence: 99%

Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases

Kitchen

Vaughn

2007

Vaccine

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Safety and immunogenicity testing of an intranasal group B meningococcal native outer membrane vesicle vaccine in healthy volunteers

Cited by 65 publications

References 24 publications

A Non-Living Nasal Influenza Vaccine Can Induce Major Humoral and Cellular Immune Responses in Humans without the Need for Adjuvants

A Non-Living Nasal Influenza Vaccine Can Induce Major Humoral and Cellular Immune Responses in Humans without the Need for Adjuvants

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

Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases

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