Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-08-31
2004-02-17
Devi, S. (Department: 1645)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C424S234100, C424S184100, C424S250100, C435S320100, C435S071100, C435S069300
Reexamination Certificate
active
06693186
ABSTRACT:
INTRODUCTION
The present invention relates generally to a polypeptide of
Neisseria meningitidis
of approximately 40-55 kD referred to as “NMASP”. The invention encompasses an isolated or purified NMASP polypeptide and polypeptides, including fragments, derived therefrom (NMASP-derived polypeptides), and methods of making thereof. The invention also encompasses antibodies, including cytotoxic or bactericidal antibodies, that specifically bind the NMASP polypeptide, NMASP-derived polypeptides and/or fragments thereof. The invention further encompasses immunogenic, prophylactic or therapeutic compositions, including vaccines, that comprise NMASP polypeptide, NMASP-derived polypeptides and/or fragments thereof. The invention additionally provides methods of inducing an immune response to
Neisseria meningitidis
in an animal and methods of treating infections in an animal caused by
Neisseria meningitidis
The invention further provides isolated nucleotide sequences encoding the NMASP polypeptide, NMASP-derived polypeptides and fragments thereof, vectors having said sequences, and host cells containing said vectors.
BACKGROUND OF THE INVENTION
Neisseriae are gram-negative diplococci and include but are not limited to
Neisseria ovis, Neisseria lacunata, Neisseria osloensis, Neisseria bovis, Neisseria meningitidis
, and
Neisseria gonorrhoeae. Neisseria meningitidis
(“N.m.”) is the most common cause of bacterial meningitidis and septicemia in infants and young adults in the industrialized world; markedly so in countries that have initiated immunization programs against
Haemophilus influenzae
type B (Hib) disease (Riedo, F. X. et al. 1995. Epidemiology and prevention of meningococcal disease.
Pediatr. Infect. Did. J
. 14:643-657; Hart, C. A. And T. R. Rogers. 1993. Meningococcal disease.
J. Med. Microbiol
. 39:3-25; Jackson, L. A. And J. D. Wenger. 1993. Laboratory-based surveillance for meningococcal disease in selected areas, United States, 1989-1991
. MMWR
42:21-30). World-wide,
N. meningitidis
accounts for about ⅓ of all cases of bacterial meningitis; with most countries showing an attack rate of >1/100,000 population. Mortality as a whole is significantly higher with the meningococci than with Hib disease. Unlike Hib infections which are basically sporadic limited outbreaks, epidemics of meningococcal disease occur regularly throughout the world and cause great suffering and death. Attack rates during epidemics can exceed 600/100,000 (Hart, C. A. And T. R. Rogers. 1993. Meningococcal disease.
J. Med. Microbiol
. 39:3-25; Jones, D. 1995. Epidemiology of meningococcal disease in Europe and the USA. In:
Meningococcal Disease
. Cartwright, K. (Ed.) Wiley Press, New York, USA: 145-157). Despite the organism's sensitivity to a wide variety of antibiotics and the impact antibiotic intervention has had on the overall case fatality rate, meningococcal disease attack rates have changed very little since the introduction of antibacterials and the fatality rate still remains between 7 and 15% even in industrialized countries.
N.m. infection starts with colonization of the upper respiratory tract; primarily the tonsils and nasopharynx (Brandtzaeg, P. 1995. Pathogenesis of meningococcal infections. In:
Meningococcal Disease
. Cartwright, K. (Ed.), Wiley Press, New York, USA: 145-157). Once colonization is established, the organism can invade the underlying endothelium and gain entry into the circulatory system where it causes a rapid, fulminate meningococcemia and/or progresses to the cerebrospinal fluid to cause an often fatal meningitis. To reach the meninges, the organism must interact and circumvent two cellular barriers, the nasopharynx and the blood-brain barrier. Bacterial-host cell interactions are thus critical for the pathogenesis of N.m. Pili, cell surface attachment components, and the polysaccharide capsule all play essential roles in the initial attachment and colonization processes (Jerse, A. E. And R. F. Rest. 1997. Adhesion and invasion by the pathogenic neisseria.
Trends Microbiol
.:217-221). Once colonization of the upper respiratory tract has been achieved, the organism can down-regulate pili expression and capsule synthesis and expresses other afimbrial adhesins and invasion proteins possibly masked by the capsule that allow the bacteria to invade the underlying endothelial cells.
Based on the structural carbohydrate composition of the meningococcal capsular polysaccharide (CPS), N.m. strains can be divided into a least 12 serogroups, designated types A through L (Riedo, F. X. et al. 1995. Epidemiology and prevention of meningococcal disease.
Pediatr. Infect. Did. J
. 14:643-657; Hart, C. A. and T. R. Rogers. 1993. Meningococcal disease.
J. Med. Microbiol
. 39:3-25). However, serogroups A, B, and C account for over 90% of meningococcal disease and are the serotypes most often associated with epidemic disease (Jones, D. 1995. Epidemiology of meningococcal disease in Europe and the USA. In:
Meningococcal Disease
. Cartwright, K. (Ed.) Wiley Press, New York, USA: 145-157). In the United States and most developed countries, roughly half of the meningococcal meningitis cases are caused by serogroup B. The highest attack rates of type B meningococcal disease are observed in young children under the age of two with the peak incidence seen in children less than 1 year of age.
The CPS has been targeted as a prime vaccine candidate for the meningococci. Several laboratories have shown that anti-CPS antibodies promote complement-mediated killing of organisms which belong to the same but not different capsular serogroups (Gotschlich, E. C. et al. 1977. The immune responses to bacterial polysaccharides in man. In:
Antibodies in Human Diagnosis and Therapy
. Haber, E. And R. M. Krause (Eds.), Raven Press, New York, USA: 391-402). The emergence of sulfonamide-resistant organisms in military recruits spurred the development of CPS vaccines against serogroups A, C, and W. While these vaccines are highly immunogenic and effective in adults, the immune response elicited in infants is minimal and of short duration, due primarily to the fact that the very young respond poorly to T-cell-independent antigens like the CPS immunogen.
Prototype serogroup B polysaccharide vaccines have been produced but were found to be poorly immunogenic in humans and gave rise to only low avidity antibody that does not stimulate high levels of complement-mediated killing or opsonization (Frasch, C. E. 1995. Meningococcal vaccines: past, present and future. In:
Meningococcal Disease
. Cartwright, K. (Ed.) Wiley Press, New York, USA: 145-157). The poor immunogenicity of the type B CPS is believed to result from the structural similarity of the type B capsule polysaccharide to the sialic acid structures (
—
−2,8 linkage) found on the surface of human brain neural cell glycoproteins (NCAMS) (Finne, J. et al. 1983. Occurrence of alpha-2,8 linked polysialosyl units in neural cell adhesion molecules.
Biochem. Biophys. Res. Comm
. 112:482-487). The poor immune responsiveness of type B CPS and the possibility that anti-type B capsular antibody may recognize native human carbohydrate structures and possibly trigger an autoimmune sequelae has resulted in a greater emphasis on the evaluation of alternative meningococcal surface antigens as potential vaccine candidates (Poolman, J. T., et al. 1986. Class ⅓ outer membrane protein vaccine against group B, type 15, subtype 16 meningococci.
Dev. Biol. Stand
. 63:147-152; Ala'Aldeen, D. A. A., et al, 1994. Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design.
Infect. Immun
. 62:2984-2990; Gotschlich, E. C. 1991. The meningococcal serogroup B vaccine protection trials: concluding remarks at the report meeting second day.
NIPH Ann
. 14:247-250; Noronha, C. P., et al., 1995. Assessment of the direct effectiveness of BC meningococcal vaccine in Rio de Janerio, Brazil: a case-control study.
Int. J. Epidemiol
. 24:1050-1057; Boslego, J. W. Et al. 1995. Efficacy, sa
Harris Andrea M.
Jackson W. James
Antex Biologics Inc
Devi S.
Pennie & Edmonds LLP
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