Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1995 Nov;69(11):7274–7277. doi: 10.1128/jvi.69.11.7274-7277.1995

Peptide vaccine against canine parvovirus: identification of two neutralization subsites in the N terminus of VP2 and optimization of the amino acid sequence.

J I Casal 1, J P Langeveld 1, E Cortés 1, W W Schaaper 1, E van Dijk 1, C Vela 1, S Kamstrup 1, R H Meloen 1
PMCID: PMC189652  PMID: 7474152

Abstract

The N-terminal domain of the major capsid protein VP2 of canine parvovirus was shown to be an excellent target for development of a synthetic peptide vaccine, but detailed information about number of epitopes, optimal length, sequence choice, and site of coupling to the carrier protein was lacking. Therefore, several overlapping peptides based on this N terminus were synthesized to establish conditions for optimal and reproducible induction of neutralizing antibodies in rabbits. The specificity and neutralizing ability of the antibody response for these peptides were determined. Within the N-terminal 23 residues of VP2, two subsites able to induce neutralizing antibodies and which overlapped by only two glycine residues at positions 10 and 11 could be discriminated. The shortest sequence sufficient for neutralization induction was nine residues. Peptides longer than 13 residues consistently induced neutralization, provided that their N termini were located between positions 1 and 11 of VP2. The orientation of the peptides at the carrier protein was also of importance, being more effective when coupled through the N terminus than through the C terminus to keyhole limpet hemocyanin. The results suggest that the presence of amino acid residues 2 to 21 (and probably 3 to 17) of VP2 in a single peptide is preferable for a synthetic peptide vaccine.

Full Text

The Full Text of this article is available as a PDF (202.4 KB).

Selected References

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

  1. Agbandje M., McKenna R., Rossmann M. G., Strassheim M. L., Parrish C. R. Structure determination of feline panleukopenia virus empty particles. Proteins. 1993 Jun;16(2):155–171. doi: 10.1002/prot.340160204. [DOI] [PubMed] [Google Scholar]
  2. Chang S. F., Sgro J. Y., Parrish C. R. Multiple amino acids in the capsid structure of canine parvovirus coordinately determine the canine host range and specific antigenic and hemagglutination properties. J Virol. 1992 Dec;66(12):6858–6867. doi: 10.1128/jvi.66.12.6858-6867.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chapman M. S., Rossmann M. G. Structure, sequence, and function correlations among parvoviruses. Virology. 1993 Jun;194(2):491–508. doi: 10.1006/viro.1993.1288. [DOI] [PubMed] [Google Scholar]
  4. Clinton G. M., Hayashi M. The parvovirus MVM: a comparison of heavy and light particle infectivity and their density conversion in vitro. Virology. 1976 Oct 1;74(1):57–63. doi: 10.1016/0042-6822(76)90127-6. [DOI] [PubMed] [Google Scholar]
  5. Cortes E., San Martin C., Langeveld J., Meloen R., Dalsgaard K., Vela C., Casal I. Topographical analysis of canine parvovirus virions and recombinant VP2 capsids. J Gen Virol. 1993 Sep;74(Pt 9):2005–2010. doi: 10.1099/0022-1317-74-9-2005. [DOI] [PubMed] [Google Scholar]
  6. Dyrberg T., Oldstone M. B. Peptides as antigens. Importance of orientation. J Exp Med. 1986 Oct 1;164(4):1344–1349. doi: 10.1084/jem.164.4.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Langeveld J. P., Casal J. I., Cortés E., van de Wetering G., Boshuizen R. S., Schaaper W. M., Dalsgaard K., Meloen R. H. Effective induction of neutralizing antibodies with the amino terminus of VP2 of canine parvovirus as a synthetic peptide. Vaccine. 1994 Nov;12(15):1473–1480. doi: 10.1016/0264-410x(94)90158-9. [DOI] [PubMed] [Google Scholar]
  8. Langeveld J. P., Casal J. I., Osterhaus A. D., Cortés E., de Swart R., Vela C., Dalsgaard K., Puijk W. C., Schaaper W. M., Meloen R. H. First peptide vaccine providing protection against viral infection in the target animal: studies of canine parvovirus in dogs. J Virol. 1994 Jul;68(7):4506–4513. doi: 10.1128/jvi.68.7.4506-4513.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Langeveld J. P., Casal J. I., Vela C., Dalsgaard K., Smale S. H., Puijk W. C., Meloen R. H. B-cell epitopes of canine parvovirus: distribution on the primary structure and exposure on the viral surface. J Virol. 1993 Feb;67(2):765–772. doi: 10.1128/jvi.67.2.765-772.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lerner R. A., Green N., Alexander H., Liu F. T., Sutcliffe J. G., Shinnick T. M. Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3403–3407. doi: 10.1073/pnas.78.6.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Li Q., Yafal A. G., Lee Y. M., Hogle J., Chow M. Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature. J Virol. 1994 Jun;68(6):3965–3970. doi: 10.1128/jvi.68.6.3965-3970.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. López de Turiso J. A., Cortés E., Ranz A., García J., Sanz A., Vela C., Casal J. I. Fine mapping of canine parvovirus B cell epitopes. J Gen Virol. 1991 Oct;72(Pt 10):2445–2456. doi: 10.1099/0022-1317-72-10-2445. [DOI] [PubMed] [Google Scholar]
  13. Paradiso P. R., Rhode S. L., 3rd, Singer I. I. Canine parvovirus: a biochemical and ultrastructural characterization. J Gen Virol. 1982 Sep;62(Pt 1):113–125. doi: 10.1099/0022-1317-62-1-113. [DOI] [PubMed] [Google Scholar]
  14. Parrish C. R. Mapping specific functions in the capsid structure of canine parvovirus and feline panleukopenia virus using infectious plasmid clones. Virology. 1991 Jul;183(1):195–205. doi: 10.1016/0042-6822(91)90132-u. [DOI] [PubMed] [Google Scholar]
  15. Rimmelzwaan G. F., Carlson J., UytdeHaag F. G., Osterhaus A. D. A synthetic peptide derived from the amino acid sequence of canine parvovirus structural proteins which defines a B cell epitope and elicits antiviral antibody in BALB c mice. J Gen Virol. 1990 Nov;71(Pt 11):2741–2745. doi: 10.1099/0022-1317-71-11-2741. [DOI] [PubMed] [Google Scholar]
  16. Schaaper W. M., Lankhof H., Puijk W. C., Meloen R. H. Manipulation of antipeptide immune response by varying the coupling of the peptide with the carrier protein. Mol Immunol. 1989 Jan;26(1):81–85. doi: 10.1016/0161-5890(89)90023-0. [DOI] [PubMed] [Google Scholar]
  17. Tsao J., Chapman M. S., Agbandje M., Keller W., Smith K., Wu H., Luo M., Smith T. J., Rossmann M. G., Compans R. W. The three-dimensional structure of canine parvovirus and its functional implications. Science. 1991 Mar 22;251(5000):1456–1464. doi: 10.1126/science.2006420. [DOI] [PubMed] [Google Scholar]
  18. Tullis G. E., Burger L. R., Pintel D. J. The trypsin-sensitive RVER domain in the capsid proteins of minute virus of mice is required for efficient cell binding and viral infection but not for proteolytic processing in vivo. Virology. 1992 Dec;191(2):846–857. doi: 10.1016/0042-6822(92)90260-v. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES