Measles virus antigenic variations and the role of individual antigens in immunization

  • T. F. Wild


Measles remains one of the major childhood diseases. Advances in genetic manipulation make possible new approaches to vaccination. However, a number of problems need to be studied before such a vaccine could be considered for field trials. (1) Does measles virus exhibit antigenic variation and if so what is its significance in protection. (2) Which antigen (s) should be incorporated in future vaccines. In the present study we compared field isolates and vaccine virus strains using monoclonal antibodies. No antigenic variation was observed on either of the two glycoproteins, the haemagglutinin (HA) and the fusion (F) proteins. In contrast, differences were observed on the nucleoprotein (NP) and one of the epitopes distinguished wild-type and vaccine strains.

To investigate the role of the different measles virus proteins in immunization, the measles virus proteins were expressed using vaccinia virus (VV) as a vector. Immunization with the HA or F recombinants, but not the NP protected mice against a lethal challenge. Protection with the F recombinant depended on the haplotype of the animal, but a low response to this antigen could be increased by the co-expression with the NP protein. Immunization of mice with the VV-recombinants expressing the F, NP or M (matrix) proteins, but not the HA, partially protected animals from a lethal challenge with canine distemper virus. In the case of the NP and M the protection was not mediated by antibodies.


Measle Virus Antigenic Variation Canine Distemper Virus Lethal Challenge Measle Virus Infection 
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  1. 1.
    Appel MJG, Shek WR, Sheshberadaran H, Norrby E (1984) Measles virus and inactivated canine distemper virus induce incomplete immunity to canine distemper. Arch Virol 82: 73–82PubMedCrossRefGoogle Scholar
  2. 2.
    Barrett T, Shrimpton SB, Russel SEH (1985) Nucleotide sequence of the entire protein encoding region of canine distemper virus polymerase-associated (P) protein mRNA. Virus Res 3: 367–372PubMedCrossRefGoogle Scholar
  3. 3.
    Barrett T, Clarke DK, Evans SA, Rima BK (1987) The nucleotide sequence of the gene encoding the F protein of canine distemper virus: a comparison of the deduced amino acid sequence with other paramyxoviruses. Virus Res 8: 373–386PubMedCrossRefGoogle Scholar
  4. 4.
    Bellini WJ, Englund G, Rozenblatt S, Arnheiter H, Richardson CD (1985) Measles virus P gene codes for two proteins. J Virol 53: 908–919PubMedGoogle Scholar
  5. 5.
    Bellini WJ, Englund G, Richardson CD, Rozenblatt S, Lazzarini RA (1986) Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences and deduced amino acid sequences. J Virol 58: 408–416PubMedGoogle Scholar
  6. 6.
    Black FL (1991) Epidemiology of paramyxoviridae. In: Kingsbury DW (ed) The Paramyxoviruses. Plenum Press, New York, pp 509–536Google Scholar
  7. 7.
    Buckland R ,Gerald C ,Barker R ,Wild TF (1987) Fusion glycoprotein of measles virus: nucleotide sequence of the gene and comparison with other paramyxoviruses. J Gen Virol 68: 1695–1703PubMedCrossRefGoogle Scholar
  8. 8.
    Buckland R, Gerald C, Barker R ,Wild TF (1988) Cloning and sequencing of the nucleoprotein gene of measles virus (Hallé strain). Nucleic Acids Res 16: 11821PubMedCrossRefGoogle Scholar
  9. 9.
    Buckland R ,Giraudon P, Wild TF (1989) Expression of Measles virus nucleoprotein in Escherichia coli: use of deletion mutants to locate the antigenic sites. J Gen Virol 70: 435–441PubMedCrossRefGoogle Scholar
  10. 10.
    Buller RML ,Smith GL, Cremer K ,Notkins AL, Moss B (1985) Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinasenegative phenotype. Nature 317: 813–815PubMedCrossRefGoogle Scholar
  11. 11.
    Curran MD, Clarke DK, Rima BK (1991) The nucleotide sequence of the gene encoding the attachment protein H of canine distemper virus. J Gen Virol 72: 443–447PubMedCrossRefGoogle Scholar
  12. 12.
    Drillien R. Spehner D, Kirn A, Giraudon P, Buckland R, Wild TF ,Lecocq JP (1988) Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein. Proc Natl Acad Sci USA 85: 1252–1256PubMedCrossRefGoogle Scholar
  13. 13.
    Ertl HCJ ,Dietzschold B ,Gore M ,Otuosjr L ,Larson JK ,Wunner WH ,Koprowski H (1989) Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. J Virol 63: 2885–2892PubMedGoogle Scholar
  14. 14.
    Fulginiti VA ,Eller JJ, Downie AW, Kempe CH (1967) Altered reactivity to measles virus. Atypical measles in children previously immunized with inactivated measles virus vaccines. J Am Med Ass 202: 1075–1080CrossRefGoogle Scholar
  15. 15.
    Gerald C, Buckland R, Barker R, Freeman G, Wild TF (1986) Measles virus haemagglutinin gene: cloning ,complete sequence analysis and expression in COS cells. J Gen Virol 67: 2695–2703PubMedCrossRefGoogle Scholar
  16. 16.
    Giraudon P ,Wild TF (1981a) Monoclonal antibodies against measles virus. J Gen Virol 54: 325–332PubMedCrossRefGoogle Scholar
  17. 17.
    Giraudon P ,Wild TF (1981b) Differentiation of measles virus strains and a strain of canine distemper virus by monoclonal antibodies. J Gen Virol 57: 179–183PubMedCrossRefGoogle Scholar
  18. 18.
    Giraudon P ,Wild TF (1985) Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity. Virology 144: 46–58PubMedCrossRefGoogle Scholar
  19. 19.
    Giraudon P ,Jacquier MF ,Wild TF (1988) Antigenic analysis of African measles virus field isolates: identification and localisation of one conserved and two variable epi tope sites on the NP protein. Virus Res 18: 137–152CrossRefGoogle Scholar
  20. 20.
    Limo M ,Yilma T (1990) Molecular cloning of the rinderpest virus matrix gene: compara tive sequence analysis with other paramyxoviruses. Virology 175: 323–327PubMedCrossRefGoogle Scholar
  21. 21.
    Malvoisin E ,Wild TF (1990) Contribution of measles virus fusion protein in protective immunity: anti-F monoclonal antibodies neutralize virus infectivity and protect mice against challenge. J Virol 64: 5160–5162PubMedGoogle Scholar
  22. 22.
    Norrby E ,Enders-Ruckle G ,Ter Meulen V (1975) Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus. J Inf Dis 132: 262–269CrossRefGoogle Scholar
  23. 23.
    Norrby E ,Sheshberadaran H ,McCullough KC ,Carpenter WC ,Örvell C (1985) Is rinderpest virus the archevirus of the morbillivirus genus? Intervirology 23: 228–232PubMedCrossRefGoogle Scholar
  24. 24.
    Panum PL (1940) Observations made during the epidemic of measles on the Faroe islands in the year 1846. American Publishing Association ,New YorkGoogle Scholar
  25. 25.
    Reiss CS,Evans GA ,Margulies DH ,Seidman JG, Burakoff SJ (1983) Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or C1 domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer. Proc Natl Acad Sci USA 80: 2709–2712PubMedCrossRefGoogle Scholar
  26. 26.
    Rozenblatt S, Eizenberg O,Ben-Levy R,Lavie V,Bellini WJ (1985) Sequence homology within the morbilliviruses. J Virol 53: 684–690PubMedGoogle Scholar
  27. 27.
    Sheshberadaran H,Norrby E,McCullough KC,Carpenter WC,Örvell C (1986) The antigenic relationship between measles, canine distemper and rinderpest viruses studied with monoclonal antibodies. J Gen Virol 67: 1381–1392PubMedCrossRefGoogle Scholar
  28. 28.
    Taylor MJ, Godfrey E, Baczko K, ter Meulen V, Wild TF, Rima B (1991) Identification of several different lineages of measles virus. J Gen Virol 72:439–442CrossRefGoogle Scholar
  29. 29.
    Ter Meulen V, Loffler S, Carter MJ, Stephenson JR (1981) Antigenic characterization of measles and SSPE virus haemagglutinin by monoclonal antibodies. J Gen Virol 57:357–364PubMedCrossRefGoogle Scholar
  30. 30.
    Tite JP, Russell SM, Dougan G, O’Callaghan D, Jones I, Brownlee G, Liew FY (1988) Antiviral immunity induced by recombinant nucleoprotein of influenza A virus. I. Characterization and cross-reactivity of T cell responses. J Immunol 141: 3980–3987PubMedGoogle Scholar
  31. 31.
    Tsukiyama K, Sugiyama M, Yoshikawa Y, Yamanouchi K (1987) Molecular cloning and sequence analysis of the rinderpest virus mRNA encoding the hemagglutinin protein. Virology 160: 48–54PubMedCrossRefGoogle Scholar
  32. 32.
    Tsukiyama K, Yoshikawa Y, Yamanouchi K (1988) Fusion glycoprotein (F) of rinderpest virus: entire nucleotide sequence of the F mRNA, and several features of the F protein. Virology 164:523–530PubMedCrossRefGoogle Scholar
  33. 33.
    Van Wyke Coelingh KL, Winter C, Murphy BR (1985) Antigenic variation in the hemagglutinin-neuraminidase protein of human parainfluenza type 3 virus. Virology 143:569–583CrossRefGoogle Scholar
  34. 34.
    Wild TF, Giraudon P, Bernard A, Huppert J (1979) Isolation and characterization of a defective measles virus from a subacute sclerosing panencephalitis patient. J Med Virol 4: 103–114PubMedCrossRefGoogle Scholar
  35. 35.
    Wild TF, Malvoisin E, Buckland R (1991) Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion. J Gen Virol 72: 439–442PubMedCrossRefGoogle Scholar
  36. 36.
    Wild TF, Bernard A, Spehner D, Drillien R (1992) Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice. J Gen Virol 73: 359–367PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1993

Authors and Affiliations

  • T. F. Wild
    • 1
  1. 1.Unité d’ Immunologie et Stratégie VaccinaleInstitut PasteurLyonFrance

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