Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus.

Vaccine Branch, National Cancer Institute, National Institutes of Health, Bldg. 10-Rm 6B-09, NIH, Bethesda, MD 20892-1578, USA.
Virology (Impact Factor: 3.37). 10/2006; 352(2):390-9. DOI: 10.1016/j.virol.2006.04.040
Source: PubMed

ABSTRACT Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8(+) T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8+ T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K(b) and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Isolation of measles virus in tissue culture by Enders and colleagues in the 1960s led to the development of the first measles vaccines. An inactivated vaccine provided only short-term protection and induced poor T cell responses and antibody that did not undergo affinity maturation. The response to this vaccine primed for atypical measles, a more severe form of measles, and was withdrawn. A live attenuated virus vaccine has been highly successful in protection from measles and in elimination of endemic measles virus transmission with the use of two doses. This vaccine is administered by injection between 9 and 15 months of age. Measles control would be facilitated if infants could be immunized at a younger age, if the vaccine were thermostable, and if delivery did not require a needle and syringe. To these ends, new vaccines are under development using macaques as an animal model and various combinations of the H, F, and N viral proteins. Promising studies have been reported using DNA vaccines, subunit vaccines, and virus-vectored vaccines.
    Current topics in microbiology and immunology 02/2009; 330:191-212. · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Measles virus is a highly prevalent neurotropic virus capable of causing persistent infections within the central nervous system. We measured IgG class antibodies to measles in 820 individuals including 138 with recent onset psychosis, 378 with persistent schizophrenia, and 304 non-psychiatric controls. Levels of antibodies among the groups were compared by bivariate and by multivariate analyses and correlated with clinical and demographic variables. The level of measles antibodies in individuals with a recent onset of psychosis was greater than the level of antibodies in individuals with persistent schizophrenia or individuals without a history of a psychiatric disorder (p<.00001). The level of measles antibodies in the individuals with persistent schizophrenia was greater than the level of measles antibodies in the controls (p<.001). Recent onset of psychosis was associated with having elevated levels of measles antibodies, defined as the 90th percentile of the levels of the controls, with an odds ratio of 8.0 (95% CI 4.6, 14.0); persistent schizophrenia was associated with having this level with an odds ratio of 2.3 (95% CI 1.4, 3.7). Within the psychiatric groups, measles antibody levels were associated with age, race, and current treatment with the antipsychotic medication, olanzapine. The reasons for elevated levels of measles antibodies in the psychiatric groups are not known with certainty and should be studied in prospective investigations.
    Schizophrenia Research 06/2010; 119(1-3):89-94. · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Measles remains a major cause of child mortality, in part due to an inability to vaccinate young infants with the current live attenuated virus vaccine (LAV). To explore new approaches to infant vaccination, chimeric Venezuelan equine encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the hemagglutinin (H) and fusion (F) proteins of measles virus (MV). Juvenile rhesus macaques vaccinated intradermally with a single dose of VEE/SIN expressing H or H and F proteins (VEE/SIN-H or VEE/SIN-H+F, respectively) developed high titers of MV-specific neutralizing antibody and gamma-interferon (IFN-gamma)-producing T cells. Infant macaques vaccinated with two doses of VEE/SIN-H+F also developed neutralizing antibody and IFN-gamma-producing T cells. Control animals were vaccinated with LAV or with a formalin-inactivated measles vaccine (FIMV). Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not. Antibody was boosted by challenge in all groups. T-cell responses to challenge were biphasic, with peaks at 7 to 25 days and at 90 to 110 days in all groups, except for the LAV group. Recrudescent T-cell activity coincided with the presence of MV RNA in peripheral blood mononuclear cells. We conclude that VEE/SIN expressing H or H and F induces durable immune responses that protect from measles and offers a promising new approach for measles vaccination. The viral and immunological factors associated with long-term control of MV replication require further investigation.
    Journal of Virology 04/2010; 84(8):3798-807. · 5.08 Impact Factor

Full-text (2 Sources)

Available from
Jun 10, 2014