Abstract
The antibody kinetics in sera from 27 adults after three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine was studied. The vaccinees received the third dose 4 to 5 years after the first two. Antibody responses against outer membrane proteins (OMPs) and lipopolysaccharides were studied by enzyme-linked immunosorbent assay and immunoblotting and with serum bactericidal assays (SBA) with three variants of the vaccine strain, 44/76. Six weeks after the second injection, the geometric mean (GM) of the levels of immunoglobulin G (IgG) against OMVs was about sevenfold higher than that of prevaccination levels, and 74% of the vaccinees developed a greater-than-twofold rise in SBA titer. After 6 months, the GM of IgG levels declined to about threefold higher, and after 4 to 5 years it declined to about twofold higher, than that before vaccination. The third dose induced a rapid increase in SBA titers in 96% of the vaccinees, and the GM of levels of IgG against OMVs rose to about 14-fold the prevaccination level. One year later, the IgG antibody levels had dropped to 4.6-fold the prevaccination level, but 88% of the vaccinees still showed bactericidal activity. The response after the two first doses was higher in individuals with prevaccination antibodies, but no such effect was found after three doses. The use of defined mutants in SBA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Opc and class 1 proteins made the most important single contributions to the bactericidal activity against the vaccine strain, but it also demonstrated the importance of antibodies against other antigens. After three doses, 68% of the vaccinees showed a significant SBA response against a strain lacking both the Opc and the class 1 proteins. Three doses converted almost all subjects to SBA responders and gave higher antibody levels and relatively less serosubtype-specific bactericidal activity than did two doses, probably indicating a broader cross-protection against heterologous strains.
Full Text
The Full Text of this article is available as a PDF (397.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aase A., Bjune G., Høiby E. A., Rosenqvist E., Pedersen A. K., Michaelsen T. E. Comparison among opsonic activity, antimeningococcal immunoglobulin G response, and serum bactericidal activity against meningococci in sera from vaccinees after immunization with a serogroup B outer membrane vesicle vaccine. Infect Immun. 1995 Sep;63(9):3531–3536. doi: 10.1128/iai.63.9.3531-3536.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Achtman M., Neibert M., Crowe B. A., Strittmatter W., Kusecek B., Weyse E., Walsh M. J., Slawig B., Morelli G., Moll A. Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A. J Exp Med. 1988 Aug 1;168(2):507–525. doi: 10.1084/jem.168.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ala'Aldeen D. A., Davies H. A., Borriello S. P. Vaccine potential of meningococcal FrpB: studies on surface exposure and functional attributes of common epitopes. Vaccine. 1994 May;12(6):535–541. doi: 10.1016/0264-410x(94)90314-x. [DOI] [PubMed] [Google Scholar]
- Ala'Aldeen D. A., Stevenson P., Griffiths E., Gorringe A. R., Irons L. I., Robinson A., Hyde S., Borriello S. P. Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design. Infect Immun. 1994 Jul;62(7):2984–2990. doi: 10.1128/iai.62.7.2984-2990.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aoun L., Lavitola A., Aubert G., Prère M. F., Cremieux A. C., Martin P. M. Human antibody response to the 70-Kd common neisserial antigen in patients and carriers of meningococci or non-pathogenic Neisseria. Ann Inst Pasteur Microbiol. 1988 Mar-Apr;139(2):203–212. [PubMed] [Google Scholar]
- Bjune G., Closs O., Frøholm L. O., Grønnesby J. K., Høiby E. A., Nøkleby H. Design of clinical trials with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway. NIPH Ann. 1991 Dec;14(2):81–93. [PubMed] [Google Scholar]
- Bjune G., Grønnesby J. K., Høiby E. A., Closs O., Nøkleby H. Results of an efficacy trial with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway. NIPH Ann. 1991 Dec;14(2):125–132. [PubMed] [Google Scholar]
- Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H., Rosenqvist E. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet. 1991 Nov 2;338(8775):1093–1096. doi: 10.1016/0140-6736(91)91961-s. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Bryn K., Kierulf P., Ovstebø R., Namork E., Aase B., Jantzen E. Meningococcal endotoxin in lethal septic shock plasma studied by gas chromatography, mass-spectrometry, ultracentrifugation, and electron microscopy. J Clin Invest. 1992 Mar;89(3):816–823. doi: 10.1172/JCI115660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brooks J. L., Rosenqvist E., Bjune G., Lambden P. R., Heckels J. E. Comparison of the class-1 outer membrane protein from B:15:P1.16 Neisseria meningitidis strains isolated from patients previously immunized with a serogroup B outer membrane protein vaccine in Norway. Microb Pathog. 1994 Dec;17(6):425–430. doi: 10.1006/mpat.1994.1087. [DOI] [PubMed] [Google Scholar]
- Delvig A. A., Wedege E., Caugant D. A., Dalseg R., Kolberg J., Achtman M., Rosenqvist E. A linear B-cell epitope on the class 3 outer-membrane protein of Neisseria meningitidis recognized after vaccination with the Norwegian group B outer-membrane vesicle vaccine. Microbiology. 1995 Jul;141(Pt 7):1593–1600. doi: 10.1099/13500872-141-7-1593. [DOI] [PubMed] [Google Scholar]
- Delvig A., Jahn S., Kusecek B., Heckels J. E., Rosenqvist E., Høiby E. A., Michaelsen T. E., Achtman M. A comparison of human and murine monoclonal IgGs specific for the P1.7 PorA protein of Neisseria meningitidis. Mol Immunol. 1994 Nov;31(16):1257–1267. doi: 10.1016/0161-5890(94)90076-0. [DOI] [PubMed] [Google Scholar]
- Frasch C. E., Zahradnik J. M., Wang L. Y., Mocca L. F., Tsai C. M. Antibody response of adults to an aluminum hydroxide-adsorbed Neisseria meningitidis serotype 2b protein-group B polysaccharide vaccine. J Infect Dis. 1988 Oct;158(4):710–718. doi: 10.1093/infdis/158.4.710. [DOI] [PubMed] [Google Scholar]
- Frasch C. E., Zollinger W. D., Poolman J. T. Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes. Rev Infect Dis. 1985 Jul-Aug;7(4):504–510. doi: 10.1093/clinids/7.4.504. [DOI] [PubMed] [Google Scholar]
- Fredriksen J. H., Rosenqvist E., Wedege E., Bryn K., Bjune G., Frøholm L. O., Lindbak A. K., Møgster B., Namork E., Rye U. Production, characterization and control of MenB-vaccine "Folkehelsa": an outer membrane vesicle vaccine against group B meningococcal disease. NIPH Ann. 1991 Dec;14(2):67–80. [PubMed] [Google Scholar]
- Frøholm L. O., Caugant D. A., Holten E., Høiby E. A., Rosenqvist E., Wedege E. Meningococcal strains isolated from teenage patients during the serogroup B vaccination trial in Norway: serotyping, serosubtyping, immunotyping and clonal analysis. NIPH Ann. 1991 Dec;14(2):139–146. [PubMed] [Google Scholar]
- Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
- Garred P., Michaelsen T. E., Bjune G., Thiel S., Svejgaard A. A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease. Scand J Immunol. 1993 Apr;37(4):468–470. doi: 10.1111/j.1365-3083.1993.tb03320.x. [DOI] [PubMed] [Google Scholar]
- Griffiss J. M. Bactericidal activity of meningococcal antisera. Blocking by IgA of lytic antibody in human convalescent sera. J Immunol. 1975 Jun;114(6):1779–1784. [PubMed] [Google Scholar]
- Griffiss J. M., Brandt B. L., Broud D. D., Goroff D. K., Baker C. J. Immune response of infants and children to disseminated infections with Neisseria meningitidis. J Infect Dis. 1984 Jul;150(1):71–79. doi: 10.1093/infdis/150.1.71. [DOI] [PubMed] [Google Scholar]
- Griffiss J. M., Goroff D. K. IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms. J Immunol. 1983 Jun;130(6):2882–2885. [PubMed] [Google Scholar]
- Guttormsen H. K., Wetzler L. M., Naess A. Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease. Infect Immun. 1993 Nov;61(11):4734–4742. doi: 10.1128/iai.61.11.4734-4742.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harthug S., Rosenqvist E., Høiby E. A., Gedde-Dahl T. W., Frøholm L. O. Antibody response in group B meningococcal disease determined by enzyme-linked immunosorbent assay with serotype 15 outer membrane antigen. J Clin Microbiol. 1986 Dec;24(6):947–953. doi: 10.1128/jcm.24.6.947-953.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Høgåsen K., Michaelsen T., Mellbye O. J., Bjune G. Low prevalence of complement deficiencies among patients with meningococcal disease in Norway. Scand J Immunol. 1993 Apr;37(4):487–489. doi: 10.1111/j.1365-3083.1993.tb03323.x. [DOI] [PubMed] [Google Scholar]
- Høiby E. A., Rosenqvist E., Frøholm L. O., Bjune G., Feiring B., Nøkleby H., Rønnild E. Bactericidal antibodies after vaccination with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine: a brief survey. NIPH Ann. 1991 Dec;14(2):147–156. [PubMed] [Google Scholar]
- Idänpän-Heikkilä I., Høiby E. A., Chattopadhyay P., Airaksinen U., Michaelsen T. M., Wedege E. Antibodies to meningococcal class 1 outer-membrane protein and its variable regions in patients with systemic meningococcal disease. J Med Microbiol. 1995 Nov;43(5):335–343. doi: 10.1099/00222615-43-5-335. [DOI] [PubMed] [Google Scholar]
- Jarvis G. A., Griffiss J. M. Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule. J Immunol. 1991 Sep 15;147(6):1962–1967. [PubMed] [Google Scholar]
- Jarvis G. A., Griffiss J. M. Human IgA1 initiates complement-mediated killing of Neisseria meningitidis. J Immunol. 1989 Sep 1;143(5):1703–1709. [PubMed] [Google Scholar]
- Kasper D. L., Winkelhake J. L., Brandt B. L., Artenstein M. S. Antigenic specificity of bactericidal antibodies in antisera to Neisseria meningitidis. J Infect Dis. 1973 Apr;127(4):378–387. doi: 10.1093/infdis/127.4.378. [DOI] [PubMed] [Google Scholar]
- Kim J. J., Mandrell R. E., Hu Z., Westerink M. A., Poolman J. T., Griffiss J. M. Electromorphic characterization and description of conserved epitopes of the lipooligosaccharides of group A Neisseria meningitidis. Infect Immun. 1988 Oct;56(10):2631–2638. doi: 10.1128/iai.56.10.2631-2638.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klugman K. P., Gotschlich E. C., Blake M. S. Sequence of the structural gene (rmpM) for the class 4 outer membrane protein of Neisseria meningitidis, homology of the protein to gonococcal protein III and Escherichia coli OmpA, and construction of meningococcal strains that lack class 4 protein. Infect Immun. 1989 Jul;57(7):2066–2071. doi: 10.1128/iai.57.7.2066-2071.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kornstad L., Heistøo A. L., Michaelsen T. E., Bjune G. ABH secretor status, as judged by the Lewis phenotypes, in Norwegian survivors from meningococcal disease. APMIS. 1993 Oct;101(10):791–794. doi: 10.1111/j.1699-0463.1993.tb00181.x. [DOI] [PubMed] [Google Scholar]
- Mandrell R. E., Zollinger W. D. Human immune response to meningococcal outer membrane protein epitopes after natural infection or vaccination. Infect Immun. 1989 May;57(5):1590–1598. doi: 10.1128/iai.57.5.1590-1598.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandrell R. E., Zollinger W. D. Use of a zwitterionic detergent for the restoration of the antibody-binding capacity of electroblotted meningococcal outer membrane proteins. J Immunol Methods. 1984 Feb 24;67(1):1–11. doi: 10.1016/0022-1759(84)90080-2. [DOI] [PubMed] [Google Scholar]
- Milagres L. G., Ramos S. R., Sacchi C. T., Melles C. E., Vieira V. S., Sato H., Brito G. S., Moraes J. C., Frasch C. E. Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy. Infect Immun. 1994 Oct;62(10):4419–4424. doi: 10.1128/iai.62.10.4419-4424.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moran E. E., Brandt B. L., Zollinger W. D. Expression of the L8 lipopolysaccharide determinant increases the sensitivity of Neisseria meningitidis to serum bactericidal activity. Infect Immun. 1994 Dec;62(12):5290–5295. doi: 10.1128/iai.62.12.5290-5295.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Munkley A., Tinsley C. R., Virji M., Heckels J. E. Blocking of bactericidal killing of Neisseria meningitidis by antibodies directed against class 4 outer membrane protein. Microb Pathog. 1991 Dec;11(6):447–452. doi: 10.1016/0882-4010(91)90041-8. [DOI] [PubMed] [Google Scholar]
- Nurminen M., Butcher S., Idänpän-Heikkilä I., Wahlström E., Muttilainen S., Runeberg-Nyman K., Sarvas M., Mäkelä P. H. The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity. Mol Microbiol. 1992 Sep;6(17):2499–2506. doi: 10.1111/j.1365-2958.1992.tb01426.x. [DOI] [PubMed] [Google Scholar]
- Otsuka A., Hanafusa T., Kono N., Tarui S. Lipopolysaccharide augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells. Immunology. 1991 Aug;73(4):428–432. [PMC free article] [PubMed] [Google Scholar]
- Peltola H., Safary A., Käyhty H., Karanko V., André F. E. Evaluation of two tetravalent (ACYW135) meningococcal vaccines in infants and small children: a clinical study comparing immunogenicity of O-acetyl-negative and O-acetyl-positive group C polysaccharides. Pediatrics. 1985 Jul;76(1):91–96. [PubMed] [Google Scholar]
- Poolman J. T. Polysaccharides and membrane vaccines. Adv Biotechnol Processes. 1990;13:57–86. [PubMed] [Google Scholar]
- Poolman J. T., van der Ley P. A., Wiertz E. J., Hoogerhout P. Second generation meningococcal OMP-LPS vaccines. NIPH Ann. 1991 Dec;14(2):233–241. [PubMed] [Google Scholar]
- Rice P. A., Vayo H. E., Tam M. R., Blake M. S. Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum. J Exp Med. 1986 Nov 1;164(5):1735–1748. doi: 10.1084/jem.164.5.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ritchie D. G., Nickerson J. M., Fuller G. M. Two simple programs for the analysis of data from enzyme-linked immunosorbent (ELISA) assays on a programmable desk-top calculator. Anal Biochem. 1981 Jan 15;110(2):281–290. doi: 10.1016/0003-2697(81)90193-7. [DOI] [PubMed] [Google Scholar]
- Rosenqvist E., Harthug S., Frøholm L. O., Høiby E. A., Bøvre K., Zollinger W. D. Antibody responses to serogroup B meningococcal outer membrane antigens after vaccination and infection. J Clin Microbiol. 1988 Aug;26(8):1543–1548. doi: 10.1128/jcm.26.8.1543-1548.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenqvist E., Høiby E. A., Bjune G., Bryn K., Closs O., Feiring B., Klem A., Nøkleby H., Frølm L. O. Human antibody responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine: results from ELISA studies. NIPH Ann. 1991 Dec;14(2):169–181. [PubMed] [Google Scholar]
- Rosenqvist E., Høiby E. A., Wedege E., Caugant D. A., Frøholm L. O., McGuinness B. T., Brooks J., Lambden P. R., Heckels J. E. A new variant of serosubtype P1.16 in Neisseria meningitidis from Norway, associated with increased resistance to bactericidal antibodies induced by a serogroup B outer membrane protein vaccine. Microb Pathog. 1993 Sep;15(3):197–205. doi: 10.1006/mpat.1993.1070. [DOI] [PubMed] [Google Scholar]
- Rosenqvist E., Høiby E. A., Wedege E., Kusecek B., Achtman M. The 5C protein of Neisseria meningitidis is highly immunogenic in humans and induces bactericidal antibodies. J Infect Dis. 1993 May;167(5):1065–1073. doi: 10.1093/infdis/167.5.1065. [DOI] [PubMed] [Google Scholar]
- Sacchi C. T., Gorla M. C., de Lemos A. P., Brandileone M. C. Considerations on the use of Neisseria meningitidis class 5 proteins as meningococcal BC vaccine components. Vaccine. 1995 Jan;13(1):112–118. doi: 10.1016/0264-410x(95)80021-5. [DOI] [PubMed] [Google Scholar]
- Saukkonen K., Abdillahi H., Poolman J. T., Leinonen M. Protective efficacy of monoclonal antibodies to class 1 and class 3 outer membrane proteins of Neisseria meningitidis B:15:P1.16 in infant rat infection model: new prospects for vaccine development. Microb Pathog. 1987 Oct;3(4):261–267. doi: 10.1016/0882-4010(87)90059-3. [DOI] [PubMed] [Google Scholar]
- Saukkonen K., Leinonen M., Abdillahi H., Poolman J. T. Comparative evaluation of potential components for group B meningococcal vaccine by passive protection in the infant rat and in vitro bactericidal assay. Vaccine. 1989 Aug;7(4):325–328. doi: 10.1016/0264-410x(89)90194-1. [DOI] [PubMed] [Google Scholar]
- Sierra G. V., Campa H. C., Varcacel N. M., Garcia I. L., Izquierdo P. L., Sotolongo P. F., Casanueva G. V., Rico C. O., Rodriguez C. R., Terry M. H. Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NIPH Ann. 1991 Dec;14(2):195–210. [PubMed] [Google Scholar]
- Skevakis L., Frasch C. E., Zahradnik J. M., Dolin R. Class-specific human bactericidal antibodies to capsular and noncapsular surface antigens of Neisseria meningitidis. J Infect Dis. 1984 Mar;149(3):387–396. doi: 10.1093/infdis/149.3.387. [DOI] [PubMed] [Google Scholar]
- Tsai C. M., Frasch C. E., Mocca L. F. Five structural classes of major outer membrane proteins in Neisseria meningitidis. J Bacteriol. 1981 Apr;146(1):69–78. doi: 10.1128/jb.146.1.69-78.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Der Ley P., Poolman J. T. Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. Infect Immun. 1992 Aug;60(8):3156–3161. doi: 10.1128/iai.60.8.3156-3161.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verheul A. F., Snippe H., Poolman J. T. Meningococcal lipopolysaccharides: virulence factor and potential vaccine component. Microbiol Rev. 1993 Mar;57(1):34–49. doi: 10.1128/mr.57.1.34-49.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verheul A. F., Van Gaans J. A., Wiertz E. J., Snippe H., Verhoef J., Poolman J. T. Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants. Infect Immun. 1993 Jan;61(1):187–196. doi: 10.1128/iai.61.1.187-196.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wedege E., Bjune G., Frøholm L. O., Høiby E. A., Rosenqvist E. Immunoblotting studies of vaccinee and patient sera from a Norwegian serogroup B meningococcal vaccination trial. NIPH Ann. 1991 Dec;14(2):183–186. [PubMed] [Google Scholar]
- Wedege E., Bryn K., Frøholm L. O. Restoration of antibody binding to blotted meningococcal outer membrane proteins using various detergents. J Immunol Methods. 1988 Oct 4;113(1):51–59. doi: 10.1016/0022-1759(88)90381-x. [DOI] [PubMed] [Google Scholar]
- Wedege E., Frøholm L. O. Human antibody response to a group B serotype 2a meningococcal vaccine determined by immunoblotting. Infect Immun. 1986 Feb;51(2):571–578. doi: 10.1128/iai.51.2.571-578.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wedege E., Høiby E. A., Rosenqvist E., Frøholm L. O. Serotyping and subtyping of Neisseria meningitidis isolates by co-agglutination, dot-blotting and ELISA. J Med Microbiol. 1990 Mar;31(3):195–201. doi: 10.1099/00222615-31-3-195. [DOI] [PubMed] [Google Scholar]
- Wyle F. A., Artenstein M. S., Brandt B. L., Tramont E. C., Kasper D. L., Altieri P. L., Berman S. L., Lowenthal J. P. Immunologic response of man to group B meningococcal polysaccharide vaccines. J Infect Dis. 1972 Nov;126(5):514–521. doi: 10.1093/infdis/126.5.514. [DOI] [PubMed] [Google Scholar]
- Zollinger W. D., Boslego J., Moran E., Garcia J., Cruz C., Ruiz S., Brandt B., Martinez M., Arthur J., Underwood P. Meningococcal serogroup B vaccine protection trial and follow-up studies in Chile. The Chilean National Committee for Meningococcal Disease. NIPH Ann. 1991 Dec;14(2):211–213. [PubMed] [Google Scholar]
- Zollinger W. D., Mandrell R. E., Griffiss J. M., Altieri P., Berman S. Complex of meningococcal group B polysaccharide and type 2 outer membrane protein immunogenic in man. J Clin Invest. 1979 May;63(5):836–848. doi: 10.1172/JCI109383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zollinger W. D., Mandrell R. E. Importance of complement source in bactericidal activity of human antibody and murine monoclonal antibody to meningococcal group B polysaccharide. Infect Immun. 1983 Apr;40(1):257–264. doi: 10.1128/iai.40.1.257-264.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zollinger W. D., Moran E. E., Connelly H., Mandrell R. E., Brandt B. Monoclonal antibodies to serotype 2 and serotype 15 outer membrane proteins of Neisseria meningitidis and their use in serotyping. Infect Immun. 1984 Oct;46(1):260–266. doi: 10.1128/iai.46.1.260-266.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zollinger W. D., Moran E. Meningococcal vaccines--present and future. Trans R Soc Trop Med Hyg. 1991;85 (Suppl 1):37–43. doi: 10.1016/0035-9203(91)90339-z. [DOI] [PubMed] [Google Scholar]
- van der Ley P., van der Biezen J., Hohenstein P., Peeters C., Poolman J. T. Use of transformation to construct antigenic hybrids of the class 1 outer membrane protein in Neisseria meningitidis. Infect Immun. 1993 Oct;61(10):4217–4224. doi: 10.1128/iai.61.10.4217-4224.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]