Abstract
Amino acid sequences 200-225 and 255-278 of the F protein of human respiratory syncytial virus (HRSV) are T cell epitopes (Bourgeoiset al., 1991 ; Corvaisieret al., 1993). Peptides corresponding to these two regions were synthesized and coupled with keyhole limpet haemocya-nin (KLH). The two conjugated proteins were administered intranasally to BALB/c mice alone or together with cholera toxin B (CTB). ELISAs revealed that the mixture of the conjugates with CTB increased not only the systemic response but also the mucosal immune response of the saliva. The systemic response was lower and the mucosal immune response was undetect-able in mice immunized with the conjugates on their own. These results suggest that these two peptide sequences are effective epitopes for inducing systemic and mucosal immune responses in conjunction with CTB, and may provide the basis for a nasal peptide vaccine against RSV for human use.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bastien, N., Trudel, M., and Simard, C., Complete protection of mice from respiratory syncytial virus infection following mucosal delivery of synthetic peptide vaccines.Vaccine, 17, 832–836(1999).
Bembridge, G P., Rodriguez, N., Garcia-Beato, R., Nicolson, C, Melero, J. A., and Taylor, G., Respiratory syncytial virus infection of gene gun vaccinated mice induces Th2-driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein.Vaccine, 19, 1038–1046(2000).
Bourgeois, C., Corvaisier, C., Bour, J. B., Kohli, E., and Pothier, P., Use of synthetic peptides to locate neutralizing antigenic domains on the fusion protein of respiratory syncytial virus.J. Gen. Virol., 72 (Pt 5), 1051–1058 (1991).
Chen, M., Hu, K. R., Rozell, B., Orvell, C., Morein, B., and Liljestrom, P., Vaccination with recombinant alphavirus or immune-stimulating complex antigen against respiratory syncytial virus.J. Immunol., 169, 3208–3216 (2002).
Connors, M., Collins, P. L, Firestone, C. Y, Sotnikov, A. V, Waitze, A., Davis, A. R., Hung, P. P., Chanock, R. M., and Murphy, B. R., Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia-RSV recombinants or RSV.Vaccine, 10, 475–484 (1992).
Corvaisier, C., Bourgeois, C., and Pothier, P., Cross-reactive and group-specific immune responses to a neutralizing epitope of the human respiratory syncytial virus fusion protein.Arch. Virol., 142, 1073–1086 (1997).
Corvaisier, C., Guillemin, G., Bourgeois, C, Bour, J. B., Kohli, E., and Pothier, P., Identification of T-cell epitopes adjacent to neutralizing antigenic domains on the fusion protein of respiratory syncytial virus.Res. Virol., 144, 141–150 (1993).
Crowe, J. E. Jr., Respiratory syncytial virus vaccine development.Vaccine, 20 Suppl 1, S32–37 (2001).
Day, N. D., Branigan, P. J., Liu, C., Gutshall, L. L., Luo, J., Melero, J. A., Sarisky, R. T., and Del Vecchio, A. M., Contribution of cysteine residues in the extracellular domain of the F protein of human respiratory syncytial virus to its function.Virol. J., 3, 34 (2006).
Domachowske, J. B. and Rosenberg, H. F., Respiratory syncytial virus infection: immune response, immunopathogenesis, and treatment.Clin. Microbiol. Rev., 12, 298–309 (1999).
Fischer, D., Rood, D., Barrette, R. W., Zuwallack, A., Kramer, E., Brown, F., and Silbart, L. K., Intranasal immunization of guinea pigs with an immunodominant foot-and-mouth disease virus peptide conjugate induces mucosal and humoral antibodies and protection against challenge.J. Virol., 77, 7486–91 (2003).
Fleming, J. O. and Pen, L. B., Measurement of the concentration of murine IgG monoclonal antibody in hybridoma supematants and ascites in absolute units by sensitive and reliable enzyme-linked immunosorbent assays (ELISA).J. Immunol. Methods, 110, 11–18(1988).
Goetsch, L., Gonzalez, A., Plotnicky-Gilquin, H., Haeuw, J. F., Aubry, J. P., Beck, A., Bonnefoy, J. Y, and Corvaia, N., Targeting of nasal mucosa-associated antigen-presenting cells in vivo with an outer membrane protein A derived from Klebsiella pneumoniae.Infect. Immun, 69, 6434–6444 (2001).
Goetsch, L., Plotnicky-Gilquin, H., Aubry, J. P., De-Lys, P., Haeuw, J. F., Bonnefoy, J. Y, Nguyen, N. T., Corvaia, N., and Velin, D., BBG2Na an RSV subunit vaccine candidate intramuscularly injected to human confers protection against viral challenge after nasal immunization in mice.Vaccine, 19, 4036–4042(2001).
Goetsch, L., Plotnicky-Gilquin, H., Champion, T., Beck, A., Corvaia, N., Stahl, S., Bonnefoy, J. Y., Nguyen, T. N., and Power, U. F., Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunit vaccine candidate.Vaccine, 18, 2735–2742 (2000).
Gonzalez-Reyes, L., Ruiz-Arguello, M. B., Garcia-Barreno, B., Calder, L., Lopez, J. A., Albar, J. P., Skehel, J. J., Wiley, D. C., and Melero, J. A., Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion.Proc. Natl. Acad. Sci. U.S.A., 98, 9859–9864 (2001).
Herd, K. A., Mahalingam, S., Mackay, I. M., Nissen, M., Sloots, T. P., and Tindle, R. W., Cytotoxic T-lymphocyte epitope vaccination protects against human metapneumovirus infection and disease in mice.J.Virol, 80, 2034–2044 (2006).
Isaka, M., Yasuda, Y, Mizokami, M., Kozuka, S., Taniguchi, T., Matano, K., Maeyama, J., Mizuno, K., Morokuma, K., Ohkuma, K., Goto, N., and Tochikubo, K., Mucosal immunization against hepatitis B virus by intranasal co-administration of recombinant hepatitis B surface artigen and recombinant cholera toxin B subunit as an adjuvant.Vaccine, 19, 1460–1466(2001).
Johnson, T. R., Teng, M. N., Collins, P. L, and Graham, B. S., Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV.J. Virol., 78, 6024–6032 (2004).
Marinaro, M., Boyaka, P. N., Kiyono, H., and McGhee, J. R., Novel approaches for the induction of T helper 1 (Th1)- or Th2-type mucosal and parenteral immune responses.Expert. Opin. Investig Drugs, 7, 1657–1666 (1998).
Martinez-Sobrido, L, Gitiban, N., Fernandez-Sesma, A., Cros, J., Mertz, S. E., Jewell, N. A., Hammond, S., Flano, E., Durbin, R. K., Garcia-Sastre, A., and Durbin, J. E., Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector.J. Virol., 80, 1130–1139 (2006).
Oien, N. L, Brideau, R. J., Walsh, E. E., and Wathen, M. W., Induction of local and systemic immunity against human respiratory syncytial virus using a chimeric FG glycoprotein and cholera toxin B subunit.Vaccine, 12, 731–735 (1994).
Paramore, L. C, Ciuryla, V, Ciesla, G, and Liu, L., Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases.Pharmacoeconomics, 22, 275–284 (2004).
Piedra, P. A., Clinical experience with respiratory syncytial virus vaccines.Pediatr. Infect. Dis. J., 22, S94–9 (2003).
Sparer, T. E., Matthews, S., Hussell, T., Rae, A. J., Garcia-Barreno, B., Melero, J. A., and Openshaw, P. J., Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia.J. Exp. Med., 187, 1921–1926 (1998).
Stambas, J., Pietersz, G, McKenzie, I., and Cheers, C., Oxidised mannan as a novel adjuvant inducing mucosal IgA production.Vaccine, 20, 1068–1078 (2002).
Tebbey, P. W., Hagen, M., and Hancock, G. E., Atypical pulmonary eosinophilia is mediated by a specific amino acid sequence of the attachment (G) protein of respiratory syncytial virus.J. Exp. Med., 188, 1967–1972 (1998).
Tebbey, P. W., Scheuer, C. A., Peek, J. A., Zhu, D., LaPierre, N. A., Green, B. A., Phillips, E. D., Ibraghimov, A. R., Eldridge, J. H., and Hancock, G E., Effective mucosal immunization against respiratory syncytial virus using purified F protein and a genetically detoxified cholera holotoxin, CT-E29H.Vaccine, 18, 2723–2734 (2000).
Techaarpornkul, S., Collins, P. L, and Peeples, M. E., Respiratory syncytial virus with the fusion protein as its only viral glycoprotein is less dependent on cellular glycosaminoglycans for attachment than complete virus.Virology, 294, 296–304 (2002).
Wathen, M. W., Brideau, R. J., Thomsen, D. R., and Murphy, B. R., Characterization of a novel human respiratory syncytial virus chimeric FG glycoprotein expressed using a baculovirus vector.J. Gen. Virol., 70 (Pt 10), 2625–2635 (1989).
Zimmer, G., Budz, L., and Herrler, G., Proteolytic activation of respiratory syncytial virus fusion protein. Cleavage at two furin consensus sequences.J. Biol. Chem., 276, 31642–50 (2001).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, H.J., Kim, JK., Seo, S.B. et al. Intranasal vaccination with peptides and cholera toxin subunit B as Adjuvant to enhance mucosal and systemic immunity to respiratory syncytial virus. Arch Pharm Res 30, 366–371 (2007). https://doi.org/10.1007/BF02977620
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02977620