Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jun;64(6):1900–1905. doi: 10.1128/iai.64.6.1900-1905.1996

Evaluation of purified UspA from Moraxella catarrhalis as a vaccine in a murine model after active immunization.

D Chen 1, J C McMichael 1, K R VanDerMeid 1, D Hahn 1, T Mininni 1, J Cowell 1, J Eldridge 1
PMCID: PMC174014  PMID: 8675285

Abstract

Moraxella catarrhalis causes otitis media, laryngitis, and respiratory infections in humans. A high-molecular-weight outer membrane protein from this bacterium named ubiquitous surface protein A (UspA) is present on all isolates. A monoclonal antibody (MAb) to UspA that recognizes a conserved epitope of this protein has been shown to promote pulmonary clearance of bacteria in passively immunized mice. In the present study, M. catarrhalis heterologous isolates were screened by dot blot with a panel of four additional MAbs specific for surface-exposed epitopes of UspA from M. catarrhalis isolate 035E. Three of the MAbs were specific for 035E, and the fourth reacted with 17 (74%) of the 23 isolates tested. Thus, UspA contains highly conserved, semiconserved, and variable surface-exposed epitopes. The UspA was purified from the 035E isolate by ion-exchange and size-exclusion chromatography, formulated with the adjuvant QS-21, and used to immunize BALB/c mice. Upon pulmonary challenge with either 035E or the heterologous isolate TTA24, significantly fewer bacteria were recovered from the lungs of immunized mice 6 h postchallenge than from control mice. The immune sera from mice or guinea pigs contained high titers of antibodies to the homologous isolate and heterologous isolates in a whole-bacterial-cell enzyme-linked immunosorbent assay. Sera against UspA, whether prepared in mice or guinea pigs, had complement-dependent bactericidal activity toward homologous and 11 heterologous M. catarrhalis isolates. These results indicate that the conserved epitopes of the UspA are highly immunogenic and elicit broadly reactive and biologically functional antibodies. UspA may offer protection against M. catarrhalis infections and is being further evaluated as a vaccine candidate.

Full Text

The Full Text of this article is available as a PDF (271.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmed K., Masaki H., Dai T. C., Ichinose A., Utsunomiya Y., Tao M., Nagatake T., Matsumoto K. Expression of fimbriae and host response in Branhamella catarrhalis respiratory infections. Microbiol Immunol. 1994;38(10):767–771. doi: 10.1111/j.1348-0421.1994.tb01855.x. [DOI] [PubMed] [Google Scholar]
  2. Ahmed K., Rikitomi N., Nagatake T., Matsumoto K. Ultrastructural study on the adherence of Branhamella catarrhalis to oropharyngeal epithelial cell. Microbiol Immunol. 1992;36(6):563–573. doi: 10.1111/j.1348-0421.1992.tb02056.x. [DOI] [PubMed] [Google Scholar]
  3. Bluestone C. D., Stephenson J. S., Martin L. M. Ten-year review of otitis media pathogens. Pediatr Infect Dis J. 1992 Aug;11(8 Suppl):S7–11. doi: 10.1097/00006454-199208001-00002. [DOI] [PubMed] [Google Scholar]
  4. Catlin B. W. Branhamella catarrhalis: an organism gaining respect as a pathogen. Clin Microbiol Rev. 1990 Oct;3(4):293–320. doi: 10.1128/cmr.3.4.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chapman A. J., Jr, Musher D. M., Jonsson S., Clarridge J. E., Wallace R. J., Jr Development of bactericidal antibody during Branhamella catarrhalis infection. J Infect Dis. 1985 May;151(5):878–882. doi: 10.1093/infdis/151.5.878. [DOI] [PubMed] [Google Scholar]
  6. Christensen J. J., Renneberg J., Bruun B., Forsgren A. Serum antibody response to proteins of Moraxella (Branhamella) catarrhalis in patients with lower respiratory tract infection. Clin Diagn Lab Immunol. 1995 Jan;2(1):14–17. doi: 10.1128/cdli.2.1.14-17.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davies B. I., Maesen F. P. The epidemiology of respiratory tract pathogens in southern Netherlands. Eur Respir J. 1988 May;1(5):415–420. [PubMed] [Google Scholar]
  8. DiGiovanni C., Riley T. V., Hoyne G. F., Yeo R., Cooksey P. Respiratory tract infections due to Branhamella catarrhalis: epidemiological data from Western Australia. Epidemiol Infect. 1987 Oct;99(2):445–453. doi: 10.1017/s0950268800067947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doyle W. J. Animal models of otitis media: other pathogens. Pediatr Infect Dis J. 1989 Jan;8(1 Suppl):S45–S47. [PubMed] [Google Scholar]
  10. Ejlertsen T. Pharyngeal carriage of Moraxella (Branhamella) catarrhalis in healthy adults. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):89–89. doi: 10.1007/BF01964414. [DOI] [PubMed] [Google Scholar]
  11. Faden H., Harabuchi Y., Hong J. J. Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media. J Infect Dis. 1994 Jun;169(6):1312–1317. doi: 10.1093/infdis/169.6.1312. [DOI] [PubMed] [Google Scholar]
  12. Fung C. P., Yeo S. F., Livermore D. M. Susceptibility of Moraxella catarrhalis isolates to beta-lactam antibiotics in relation to beta-lactamase pattern. J Antimicrob Chemother. 1994 Feb;33(2):215–222. doi: 10.1093/jac/33.2.215. [DOI] [PubMed] [Google Scholar]
  13. Goldblatt D., Turner M. W., Levinsky R. J. Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood. J Infect Dis. 1990 Nov;162(5):1128–1135. doi: 10.1093/infdis/162.5.1128. [DOI] [PubMed] [Google Scholar]
  14. Helminen M. E., Beach R., Maciver I., Jarosik G., Hansen E. J., Leinonen M. Human immune response against outer membrane proteins of Moraxella (Branhamella) catarrhalis determined by immunoblotting and enzyme immunoassay. Clin Diagn Lab Immunol. 1995 Jan;2(1):35–39. doi: 10.1128/cdli.2.1.35-39.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Helminen M. E., Maciver I., Latimer J. L., Cope L. D., McCracken G. H., Jr, Hansen E. J. A major outer membrane protein of Moraxella catarrhalis is a target for antibodies that enhance pulmonary clearance of the pathogen in an animal model. Infect Immun. 1993 May;61(5):2003–2010. doi: 10.1128/iai.61.5.2003-2010.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Helminen M. E., Maciver I., Latimer J. L., Klesney-Tait J., Cope L. D., Paris M., McCracken G. H., Jr, Hansen E. J. A large, antigenically conserved protein on the surface of Moraxella catarrhalis is a target for protective antibodies. J Infect Dis. 1994 Oct;170(4):867–872. doi: 10.1093/infdis/170.4.867. [DOI] [PubMed] [Google Scholar]
  17. Klingman K. L., Murphy T. F. Purification and characterization of a high-molecular-weight outer membrane protein of Moraxella (Branhamella) catarrhalis. Infect Immun. 1994 Apr;62(4):1150–1155. doi: 10.1128/iai.62.4.1150-1155.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Maciver I., Unhanand M., McCracken G. H., Jr, Hansen E. J. Effect of immunization of pulmonary clearance of Moraxella catarrhalis in an animal model. J Infect Dis. 1993 Aug;168(2):469–472. doi: 10.1093/infdis/168.2.469. [DOI] [PubMed] [Google Scholar]
  20. Murphy T. F., Bartos L. C. Surface-exposed and antigenically conserved determinants of outer membrane proteins of Branhamella catarrhalis. Infect Immun. 1989 Oct;57(10):2938–2941. doi: 10.1128/iai.57.10.2938-2941.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Murphy T. F., Kirkham C., Lesse A. J. The major heat-modifiable outer membrane protein CD is highly conserved among strains of Branhamella catarrhalis. Mol Microbiol. 1993 Oct;10(1):87–97. doi: 10.1111/j.1365-2958.1993.tb00906.x. [DOI] [PubMed] [Google Scholar]
  22. Murphy T. F., Loeb M. R. Isolation of the outer membrane of Branhamella catarrhalis. Microb Pathog. 1989 Mar;6(3):159–174. doi: 10.1016/0882-4010(89)90066-1. [DOI] [PubMed] [Google Scholar]
  23. Onofrio J. M., Shulkin A. N., Heidbrink P. J., Toews G. B., Pierce A. K. Pulmonary clearance and phagocytic cell response to normal pharyngeal flora. Am Rev Respir Dis. 1981 Feb;123(2):222–225. doi: 10.1164/arrd.1981.123.2.222. [DOI] [PubMed] [Google Scholar]
  24. Ruuskanen O., Heikkinen T. Otitis media: etiology and diagnosis. Pediatr Infect Dis J. 1994 Jan;13(1 Suppl 1):S23–S54. [PubMed] [Google Scholar]
  25. Sarubbi F. A., Myers J. W., Williams J. J., Shell C. G. Respiratory infections caused by Branhamella catarrhalis. Selected epidemiologic features. Am J Med. 1990 May 14;88(5A):9S–14S. doi: 10.1016/0002-9343(90)90254-b. [DOI] [PubMed] [Google Scholar]
  26. Schalén L., Eliasson I., Fex S., Kamme C., Schalén C. Acute laryngitis in adults: results of erythromycin treatment. Acta Otolaryngol Suppl. 1992;492:55–57. doi: 10.3109/00016489209136810. [DOI] [PubMed] [Google Scholar]
  27. Schalén L., Eliasson I., Kamme C., Schalén C. Erythromycin in acute laryngitis in adults. Ann Otol Rhinol Laryngol. 1993 Mar;102(3 Pt 1):209–214. doi: 10.1177/000348949310200308. [DOI] [PubMed] [Google Scholar]
  28. Unhanand M., Maciver I., Ramilo O., Arencibia-Mireles O., Argyle J. C., McCracken G. H., Jr, Hansen E. J. Pulmonary clearance of Moraxella catarrhalis in an animal model. J Infect Dis. 1992 Apr;165(4):644–650. doi: 10.1093/infdis/165.4.644. [DOI] [PubMed] [Google Scholar]
  29. Vaneechoutte M., Verschraegen G., Claeys G., Weise B., Van den Abeele A. M. Respiratory tract carrier rates of Moraxella (Branhamella) catarrhalis in adults and children and interpretation of the isolation of M. catarrhalis from sputum. J Clin Microbiol. 1990 Dec;28(12):2674–2680. doi: 10.1128/jcm.28.12.2674-2680.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Verghese A., Berro E., Berro J., Franzus B. W. Pulmonary clearance and phagocytic cell response in a murine model of Branhamella catarrhalis infection. J Infect Dis. 1990 Nov;162(5):1189–1192. doi: 10.1093/infdis/162.5.1189. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES