Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 May;64(5):1666–1671. doi: 10.1128/iai.64.5.1666-1671.1996

Attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria.

D E Lanar 1, J A Tine 1, C de Taisne 1, M C Seguin 1, W I Cox 1, J P Winslow 1, L A Ware 1, E B Kauffman 1, D Gordon 1, W R Ballou 1, E Paoletti 1, J C Sadoff 1
PMCID: PMC173977  PMID: 8613376

Abstract

NYVAC-based vaccinia virus recombinants expressing the circumsporozoite protein (CSP) were evaluated in the Plasmodium berghei rodent malaria model system. Immunization of mice with a NYVAC-based CSP recombinant elicited a high level of protection (60 to 100%). Protection did not correlate with CS repeat-specific antibody responses and was abrogated by in vivo CD8+ T-cell depletion. Protection was not enhanced by modification of the subcellular localization of CSP. These results suggest the potential of poxvirus-based vectors for the development of vaccine candidates for human malaria.

Full Text

The Full Text of this article is available as a PDF (416.9 KB).

Selected References

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

  1. Aggarwal A., Kumar S., Jaffe R., Hone D., Gross M., Sadoff J. Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J Exp Med. 1990 Oct 1;172(4):1083–1090. doi: 10.1084/jem.172.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballou W. R., Hoffman S. L., Sherwood J. A., Hollingdale M. R., Neva F. A., Hockmeyer W. T., Gordon D. M., Schneider I., Wirtz R. A., Young J. F. Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet. 1987 Jun 6;1(8545):1277–1281. doi: 10.1016/s0140-6736(87)90540-x. [DOI] [PubMed] [Google Scholar]
  3. Brochier B., Kieny M. P., Costy F., Coppens P., Bauduin B., Lecocq J. P., Languet B., Chappuis G., Desmettre P., Afiademanyo K. Large-scale eradication of rabies using recombinant vaccinia-rabies vaccine. Nature. 1991 Dec 19;354(6354):520–522. doi: 10.1038/354520a0. [DOI] [PubMed] [Google Scholar]
  4. Brockmeier S. L., Lager K. M., Tartaglia J., Riviere M., Paoletti E., Mengeling W. L. Vaccination of pigs against pseudorabies with highly attenuated vaccinia (NYVAC) recombinant viruses. Vet Microbiol. 1993 Dec;38(1-2):41–58. doi: 10.1016/0378-1135(93)90074-h. [DOI] [PubMed] [Google Scholar]
  5. Brunner K. T., Mauel J., Cerottini J. C., Chapuis B. Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology. 1968 Feb;14(2):181–196. [PMC free article] [PubMed] [Google Scholar]
  6. Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
  7. Coupar B. E., Andrew M. E., Both G. W., Boyle D. B. Temporal regulation of influenza hemagglutinin expression in vaccinia virus recombinants and effects on the immune response. Eur J Immunol. 1986 Dec;16(12):1479–1487. doi: 10.1002/eji.1830161203. [DOI] [PubMed] [Google Scholar]
  8. Cox W. I., Tartaglia J., Paoletti E. Induction of cytotoxic T lymphocytes by recombinant canarypox (ALVAC) and attenuated vaccinia (NYVAC) viruses expressing the HIV-1 envelope glycoprotein. Virology. 1993 Aug;195(2):845–850. doi: 10.1006/viro.1993.1442. [DOI] [PubMed] [Google Scholar]
  9. Cremer K. J., Mackett M., Wohlenberg C., Notkins A. L., Moss B. Vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D prevents latent herpes in mice. Science. 1985 May 10;228(4700):737–740. doi: 10.1126/science.2986288. [DOI] [PubMed] [Google Scholar]
  10. Deubel V., Kinney R. M., Esposito J. J., Cropp C. B., Vorndam A. V., Monath T. P., Trent D. W. Dengue 2 virus envelope protein expressed by a recombinant vaccinia virus fails to protect monkeys against dengue. J Gen Virol. 1988 Aug;69(Pt 8):1921–1929. doi: 10.1099/0022-1317-69-8-1921. [DOI] [PubMed] [Google Scholar]
  11. Egan J. E., Weber J. L., Ballou W. R., Hollingdale M. R., Majarian W. R., Gordon D. M., Maloy W. L., Hoffman S. L., Wirtz R. A., Schneider I. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science. 1987 Apr 24;236(4800):453–456. doi: 10.1126/science.3551073. [DOI] [PubMed] [Google Scholar]
  12. Goebel S. J., Johnson G. P., Perkus M. E., Davis S. W., Winslow J. P., Paoletti E. The complete DNA sequence of vaccinia virus. Virology. 1990 Nov;179(1):247-66, 517-63. doi: 10.1016/0042-6822(90)90294-2. [DOI] [PubMed] [Google Scholar]
  13. Guo P. X., Goebel S., Perkus M. E., Taylor J., Norton E., Allen G., Languet B., Desmettre P., Paoletti E. Coexpression by vaccinia virus recombinants of equine herpesvirus 1 glycoproteins gp13 and gp14 results in potentiated immunity. J Virol. 1990 May;64(5):2399–2406. doi: 10.1128/jvi.64.5.2399-2406.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herrington D. A., Clyde D. F., Losonsky G., Cortesia M., Murphy J. R., Davis J., Baqar S., Felix A. M., Heimer E. P., Gillessen D. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature. 1987 Jul 16;328(6127):257–259. doi: 10.1038/328257a0. [DOI] [PubMed] [Google Scholar]
  15. Hollingdale M. R., Zavala F., Nussenzweig R. S., Nussenzweig V. Antibodies to the protective antigen of Plasmodium berghei sporozoites prevent entry into cultured cells. J Immunol. 1982 Apr;128(4):1929–1930. [PubMed] [Google Scholar]
  16. Hu S. L., Kosowski S. G., Dalrymple J. M. Expression of AIDS virus envelope gene in recombinant vaccinia viruses. Nature. 1986 Apr 10;320(6062):537–540. doi: 10.1038/320537a0. [DOI] [PubMed] [Google Scholar]
  17. Khusmith S., Charoenvit Y., Kumar S., Sedegah M., Beaudoin R. L., Hoffman S. L. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science. 1991 May 3;252(5006):715–718. doi: 10.1126/science.1827210. [DOI] [PubMed] [Google Scholar]
  18. Konishi E., Pincus S., Paoletti E., Shope R. E., Burrage T., Mason P. W. Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. Virology. 1992 Jun;188(2):714–720. doi: 10.1016/0042-6822(92)90526-u. [DOI] [PubMed] [Google Scholar]
  19. Lal A. A., de la Cruz V. F., Good M. F., Weiss W. R., Lunde M., Maloy W. L., Welsh J. A., McCutchan T. F. In vivo testing of subunit vaccines against malaria sporozoites using a rodent system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8647–8651. doi: 10.1073/pnas.84.23.8647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lanar D. E. Sequence of the circumsporozoite gene of Plasmodium berghei ANKA clone and NK65 strain. Mol Biochem Parasitol. 1990 Feb;39(1):151–153. doi: 10.1016/0166-6851(90)90018-h. [DOI] [PubMed] [Google Scholar]
  21. Langford C. J., Edwards S. J., Smith G. L., Mitchell G. F., Moss B., Kemp D. J., Anders R. F. Anchoring a secreted plasmodium antigen on the surface of recombinant vaccinia virus-infected cells increases its immunogenicity. Mol Cell Biol. 1986 Sep;6(9):3191–3199. doi: 10.1128/mcb.6.9.3191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Li S., Rodrigues M., Rodriguez D., Rodriguez J. R., Esteban M., Palese P., Nussenzweig R. S., Zavala F. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5214–5218. doi: 10.1073/pnas.90.11.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Link H. T., Ballou W. R., Krzych U. Immune response to Plasmodium berghei sporozoite antigens. I. Evaluation of murine T cell repertoire following immunization with irradiated sporozoites. Am J Trop Med Hyg. 1990 Nov;43(5):452–463. doi: 10.4269/ajtmh.1990.43.452. [DOI] [PubMed] [Google Scholar]
  24. Mason P. W., Pincus S., Fournier M. J., Mason T. L., Shope R. E., Paoletti E. Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology. 1991 Jan;180(1):294–305. doi: 10.1016/0042-6822(91)90034-9. [DOI] [PubMed] [Google Scholar]
  25. Morgan A. J., Mackett M., Finerty S., Arrand J. R., Scullion F. T., Epstein M. A. Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas. J Med Virol. 1988 Jun;25(2):189–195. doi: 10.1002/jmv.1890250209. [DOI] [PubMed] [Google Scholar]
  26. Nussenzweig V., Nussenzweig R. S. Rationale for the development of an engineered sporozoite malaria vaccine. Adv Immunol. 1989;45:283–334. doi: 10.1016/s0065-2776(08)60695-1. [DOI] [PubMed] [Google Scholar]
  27. Panicali D., Davis S. W., Weinberg R. L., Paoletti E. Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5364–5368. doi: 10.1073/pnas.80.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Paoletti E., Lipinskas B. R., Samsonoff C., Mercer S., Panicali D. Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D. Proc Natl Acad Sci U S A. 1984 Jan;81(1):193–197. doi: 10.1073/pnas.81.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Perkus M. E., Limbach K., Paoletti E. Cloning and expression of foreign genes in vaccinia virus, using a host range selection system. J Virol. 1989 Sep;63(9):3829–3836. doi: 10.1128/jvi.63.9.3829-3836.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Potocnjak P., Yoshida N., Nussenzweig R. S., Nussenzweig V. Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980 Jun 1;151(6):1504–1513. doi: 10.1084/jem.151.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pye D., Edwards S. J., Anders R. F., O'Brien C. M., Franchina P., Corcoran L. N., Monger C., Peterson M. G., Vandenberg K. L., Smythe J. A. Failure of recombinant vaccinia viruses expressing Plasmodium falciparum antigens to protect Saimiri monkeys against malaria. Infect Immun. 1991 Jul;59(7):2403–2411. doi: 10.1128/iai.59.7.2403-2411.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Romero P. J., Tam J. P., Schlesinger D., Clavijo P., Gibson H., Barr P. J., Nussenzweig R. S., Nussenzweig V., Zavala F. Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. Eur J Immunol. 1988 Dec;18(12):1951–1957. doi: 10.1002/eji.1830181213. [DOI] [PubMed] [Google Scholar]
  33. Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
  34. Sadoff J. C., Ballou W. R., Baron L. S., Majarian W. R., Brey R. N., Hockmeyer W. T., Young J. F., Cryz S. J., Ou J., Lowell G. H. Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science. 1988 Apr 15;240(4850):336–338. doi: 10.1126/science.3281260. [DOI] [PubMed] [Google Scholar]
  35. Satchidanandam V., Zavala F., Moss B. Studies using a recombinant vaccinia virus expressing the circumsporozoite protein of Plasmodium berghei. Mol Biochem Parasitol. 1991 Sep;48(1):89–99. doi: 10.1016/0166-6851(91)90167-5. [DOI] [PubMed] [Google Scholar]
  36. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  37. Schödel F., Wirtz R., Peterson D., Hughes J., Warren R., Sadoff J., Milich D. Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying circumsporozoite protein epitopes. J Exp Med. 1994 Sep 1;180(3):1037–1046. doi: 10.1084/jem.180.3.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sedegah M., Hedstrom R., Hobart P., Hoffman S. L. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9866–9870. doi: 10.1073/pnas.91.21.9866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Seguin M. C., Klotz F. W., Schneider I., Weir J. P., Goodbary M., Slayter M., Raney J. J., Aniagolu J. U., Green S. J. Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells. J Exp Med. 1994 Jul 1;180(1):353–358. doi: 10.1084/jem.180.1.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Smith G. L., Murphy B. R., Moss B. Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7155–7159. doi: 10.1073/pnas.80.23.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tam J. P., Clavijo P., Lu Y. A., Nussenzweig V., Nussenzweig R., Zavala F. Incorporation of T and B epitopes of the circumsporozoite protein in a chemically defined synthetic vaccine against malaria. J Exp Med. 1990 Jan 1;171(1):299–306. doi: 10.1084/jem.171.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tartaglia J., Perkus M. E., Taylor J., Norton E. K., Audonnet J. C., Cox W. I., Davis S. W., van der Hoeven J., Meignier B., Riviere M. NYVAC: a highly attenuated strain of vaccinia virus. Virology. 1992 May;188(1):217–232. doi: 10.1016/0042-6822(92)90752-b. [DOI] [PubMed] [Google Scholar]
  43. Tartaglia J., Pincus S., Paoletti E. Poxvirus-based vectors as vaccine candidates. Crit Rev Immunol. 1990;10(1):13–30. [PubMed] [Google Scholar]
  44. Tine J. A., Conseil V., Delplace P., De Taisne C., Camus D., Paoletti E. Immunogenicity of the Plasmodium falciparum serine repeat antigen (p126) expressed by vaccinia virus. Infect Immun. 1993 Sep;61(9):3933–3941. doi: 10.1128/iai.61.9.3933-3941.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Townsend A., Bastin J., Gould K., Brownlee G., Andrew M., Coupar B., Boyle D., Chan S., Smith G. Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J Exp Med. 1988 Oct 1;168(4):1211–1224. doi: 10.1084/jem.168.4.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wachsman M., Aurelian L., Smith C. C., Lipinskas B. R., Perkus M. E., Paoletti E. Protection of guinea pigs from primary and recurrent herpes simplex virus (HSV) type 2 cutaneous disease with vaccinia virus recombinants expressing HSV glycoprotein D. J Infect Dis. 1987 Jun;155(6):1188–1197. doi: 10.1093/infdis/155.6.1188. [DOI] [PubMed] [Google Scholar]
  47. Weber J. L., Egan J. E., Lyon J. A., Wirtz R. A., Charoenvit Y., Maloy W. L., Hockmeyer W. T. Plasmodium berghei: cloning of the circumsporozoite protein gene. Exp Parasitol. 1987 Jun;63(3):295–300. doi: 10.1016/0014-4894(87)90176-7. [DOI] [PubMed] [Google Scholar]
  48. Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. White K. L., Jarboe D. L., Krzych U. Immunization with irradiated Plasmodium berghei sporozoites induces IL-2 and IFN gamma but not IL-4. Parasite Immunol. 1994 Sep;16(9):479–491. doi: 10.1111/j.1365-3024.1994.tb00376.x. [DOI] [PubMed] [Google Scholar]
  50. Yewdell J. W., Bennink J. R., Smith G. L., Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zarling J. M., Morton W., Moran P. A., McClure J., Kosowski S. G., Hu S. L. T-cell responses to human AIDS virus in macaques immunized with recombinant vaccinia viruses. 1986 Sep 25-Oct 1Nature. 323(6086):344–346. doi: 10.1038/323344a0. [DOI] [PubMed] [Google Scholar]
  52. Zavala F., Cochrane A. H., Nardin E. H., Nussenzweig R. S., Nussenzweig V. Circumsporozoite proteins of malaria parasites contain a single immunodominant region with two or more identical epitopes. J Exp Med. 1983 Jun 1;157(6):1947–1957. doi: 10.1084/jem.157.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zhao B. T., Prince G., Horswood R., Eckels K., Summers P., Chanock R., Lai C. J. Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus. J Virol. 1987 Dec;61(12):4019–4022. doi: 10.1128/jvi.61.12.4019-4022.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES