Profiling of Measles-Specific Humoral Immunity in Individuals Following Two Doses of MMR Vaccine Using Proteome Microarrays

Introduction: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Results: Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV) phosphoprotein (P), nucleoprotein (N), as well as antibodies to the large polymerase (L) protein (fragment 1234 to 1900 AA). Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies), were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response. Conclusion: Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.

[1]  J. Zipprich,et al.  Measles Outbreak — California, December 2014–February 2015 , 2015, MMWR. Morbidity and mortality weekly report.

[2]  G. Poland,et al.  Measles and mumps outbreaks in the United States: Think globally, vaccinate locally. , 2014, Vaccine.

[3]  W. Bellini,et al.  Outbreak of measles among persons with prior evidence of immunity, New York City, 2011. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  Marta Gacic-Dobo,et al.  Global Control and Regional Elimination of Measles, 2000–2012 , 2014, MMWR. Morbidity and mortality weekly report.

[5]  D. Molina,et al.  Protein Microarray Analysis of Antibody Responses to Plasmodium falciparum in Western Kenyan Highland Sites with Differing Transmission Levels , 2013, PloS one.

[6]  R. Fields,et al.  Moving forward with strengthening routine immunization delivery as part of measles and rubella elimination activities. , 2013, Vaccine.

[7]  Qian Li,et al.  Waning immunity to measles in young adults and booster effects of revaccination in secondary school students. , 2013, Vaccine.

[8]  Gregory A Poland,et al.  The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches , 2013, Expert review of vaccines.

[9]  P. Lopalco,et al.  Measles still spreads in Europe: who is responsible for the failure to vaccinate? , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[10]  R. Vierkant,et al.  Response surface methodology to determine optimal measles-specific cytokine responses in human peripheral blood mononuclear cells. , 2012, Journal of immunological methods.

[11]  R. Vierkant,et al.  Independence of measles-specific humoral and cellular immune responses to vaccination. , 2012, Human immunology.

[12]  D. Skowronski,et al.  Higher risk of measles when the first dose of a 2-dose schedule of measles vaccine is given at 12-14 months versus 15 months of age. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  V. Pankratz,et al.  Multigenic control of measles vaccine immunity mediated by polymorphisms in measles receptor, innate pathway, and cytokine genes. , 2012, Vaccine.

[14]  L. BenMohamed,et al.  Discovery of Potential Diagnostic and Vaccine Antigens in Herpes Simplex Virus 1 and 2 by Proteome-Wide Antibody Profiling , 2012, Journal of Virology.

[15]  V. Pankratz,et al.  Associations between demographic variables and multiple measles-specific innate and cell-mediated immune responses after measles vaccination. , 2012, Viral immunology.

[16]  D. Molina,et al.  Measurement of antibody responses to Modified Vaccinia virus Ankara (MVA) and Dryvax(®) using proteome microarrays and development of recombinant protein ELISAs. , 2012, Vaccine.

[17]  R. Jacobson,et al.  The re-emergence of measles in developed countries: time to develop the next-generation measles vaccines? , 2012, Vaccine.

[18]  R. Plemper,et al.  Independent Structural Domains in Paramyxovirus Polymerase Protein* , 2012, The Journal of Biological Chemistry.

[19]  R. Vierkant,et al.  Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine , 2012, Pharmacogenetics and genomics.

[20]  R. Vierkant,et al.  The Association of CD46, SLAM and CD209 Cellular Receptor Gene SNPs with Variations in Measles Vaccine-Induced Immune Responses: A Replication Study and Examination of Novel Polymorphisms , 2011, Human Heredity.

[21]  R. Vierkant,et al.  Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination. , 2011, Vaccine.

[22]  R. Vierkant,et al.  Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine , 2011, Vaccine.

[23]  Louis P Garrison,et al.  Global eradication of measles: an epidemiologic and economic evaluation. , 2011, The Journal of infectious diseases.

[24]  W. Bellini,et al.  Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals. , 2011, The Journal of infectious diseases.

[25]  V. Pankratz,et al.  A large observational study to concurrently assess persistence of measles specific B-cell and T-cell immunity in individuals following two doses of MMR vaccine. , 2011, Vaccine.

[26]  R. Vierkant,et al.  The role of polymorphisms in Toll-like receptors and their associated intracellular signaling genes in measles vaccine immunity , 2011, Human Genetics.

[27]  R. Vierkant,et al.  Differential cellular immune responses to wild‐type and attenuated edmonston tag measles virus strains are primarily defined by the viral phosphoprotein gene , 2010, Journal of medical virology.

[28]  B. Monk,et al.  High-throughput profiling of the humoral immune responses against thirteen human papillomavirus types by proteome microarrays. , 2010, Virology.

[29]  Philip L Felgner,et al.  Dynamic antibody responses to the Mycobacterium tuberculosis proteome , 2010, Proceedings of the National Academy of Sciences.

[30]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[31]  A. Osterhaus,et al.  Depletion of measles virus glycoprotein-specific antibodies from human sera reveals genotype-specific neutralizing antibodies. , 2009, The Journal of general virology.

[32]  C. Samuel,et al.  Mechanisms of Protein Kinase PKR-Mediated Amplification of Beta Interferon Induction by C Protein-Deficient Measles Virus , 2009, Journal of Virology.

[33]  B. Forssman,et al.  Vaccine failures and vaccine effectiveness in children during measles outbreaks in New South Wales, March-May 2006. , 2009, Communicable diseases intelligence quarterly report.

[34]  N. Andrews,et al.  Comparison of plaque reduction neutralisation test (PRNT) and measles virus-specific IgG ELISA for assessing immunogenicity of measles vaccination. , 2008, Vaccine.

[35]  A. Bennett,et al.  Laboratory methods for assessing vaccine potency retained in aerosol outputs from nebulizers: application to World Health Organization measles aerosol project. , 2008, Vaccine.

[36]  R. Vierkant,et al.  Virus Immunity Microneutralization Assay for Measles Fluorescence-based Plaque Reduction Development of a Novel Efficient , 2008 .

[37]  R. Cattaneo,et al.  Attenuation of V- or C-Defective Measles Viruses: Infection Control by the Inflammatory and Interferon Responses of Rhesus Monkeys , 2008, Journal of Virology.

[38]  Remington Nevin,et al.  Incidence of mumps and immunity to measles, mumps and rubella among US military recruits, 2000-2004. , 2008, Vaccine.

[39]  N. Andrews,et al.  Plaque reduction neutralization test for measles antibodies: Description of a standardised laboratory method for use in immunogenicity studies of aerosol vaccination. , 2007, Vaccine.

[40]  K. Komase,et al.  Development of a new neutralization test for measles virus. , 2007, Journal of virological methods.

[41]  D. Bi,et al.  Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment. , 2007, Archives of pediatrics & adolescent medicine.

[42]  W. Moss,et al.  Global measles elimination , 2006, Nature Reviews Microbiology.

[43]  N. Andrews,et al.  Measles immunity testing: comparison of two measles IgG ELISAs with plaque reduction neutralisation assay. , 2006, Journal of virological methods.

[44]  A. Osterhaus,et al.  Relative Contributions of Measles Virus Hemagglutinin- and Fusion Protein-Specific Serum Antibodies to Virus Neutralization , 2005, Journal of Virology.

[45]  Pierre Baldi,et al.  Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[46]  B. Grenfell,et al.  Waning immunity and subclinical measles infections in England. , 2004, Vaccine.

[47]  C. Pannuti,et al.  Identification of Primary and Secondary Measles Vaccine Failures by Measurement of Immunoglobulin G Avidity in Measles Cases during the 1997 São Paulo Epidemic , 2004, Clinical Diagnostic Laboratory Immunology.

[48]  C. Muller,et al.  Immunodominant domains of the Measles virus hemagglutinin protein eliciting a neutralizing human B cell response , 2003, Archives of Virology.

[49]  K. Nagata,et al.  Measles virus V protein blocks interferon (IFN)‐α/β but not IFN‐γ signaling by inhibiting STAT1 and STAT2 phosphorylation , 2003 .

[50]  W. P. Duprex,et al.  Modulating the Function of the Measles Virus RNA-Dependent RNA Polymerase by Insertion of Green Fluorescent Protein into the Open Reading Frame , 2002, Journal of Virology.

[51]  M. Billeter,et al.  V and C proteins of measles virus function as virulence factors in vivo. , 2000, Virology.

[52]  H. Whittle,et al.  Sex-Associated Differences in the Antibody-Dependent Cellular Cytotoxicity Antibody Response to Measles Vaccines , 2000, Clinical Diagnostic Laboratory Immunology.

[53]  J. Mossong,et al.  Modeling the impact of subclinical measles transmission in vaccinated populations with waning immunity. , 1999, American journal of epidemiology.

[54]  B. Ward,et al.  Measurement of measles virus-specific neutralizing antibodies: evaluation of the syncytium inhibition assay in comparison with the plaque reduction neutralization test. , 1999, Diagnostic microbiology and infectious disease.

[55]  O. Heinonen,et al.  Explosive school-based measles outbreak: intense exposure may have resulted in high risk, even among revaccinees. , 1998, American journal of epidemiology.

[56]  D. Schaid,et al.  The association between HLA class I alleles and measles vaccine-induced antibody response: evidence of a significant association. , 1998, Vaccine.

[57]  G. Landucci,et al.  In vitro reduction of virus infectivity by antibody-dependent cell-mediated immunity. , 1998, Journal of immunological methods.

[58]  M. Billeter,et al.  Expression of Measles Virus V Protein Is Associated with Pathogenicity and Control of Viral RNA Synthesis , 1998, Journal of Virology.

[59]  P. Fournier,et al.  A simplified immunoassay based on measles virus recombinant hemagglutinin protein for testing the immune status of vaccinees. , 1998, Journal of virological methods.

[60]  C. Muller,et al.  Immunosorbent Assay Based on Recombinant Hemagglutinin Protein Produced in a High-Efficiency Mammalian Expression System for Surveillance of Measles Immunity , 1998, Journal of Clinical Microbiology.

[61]  A. Charlett,et al.  An evaluation of nine commercial EIA kits for the detection of measles specific IgG. , 1997, Journal of virological methods.

[62]  P. Wollan,et al.  Measles reimmunization in children seronegative after initial immunization. , 1997, JAMA.

[63]  V. Gadag,et al.  Comparison of commercial enzyme immunoassay kits with plaque reduction neutralization test for detection of measles virus antibody , 1995, Journal of clinical microbiology.

[64]  R. Jacobson,et al.  Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons. , 1994, Archives of internal medicine.

[65]  G. Landucci,et al.  Comparison of measles virus-specific antibodies with antibody-dependent cellular cytotoxicity and neutralizing functions. , 1993, The Journal of infectious diseases.

[66]  J. Rose,et al.  Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain disease , 1993, Journal of virology.

[67]  R Buckland,et al.  Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion. , 1991, The Journal of general virology.

[68]  Robert T. Chen,et al.  Measles antibody: reevaluation of protective titers. , 1990, The Journal of infectious diseases.

[69]  P. Albrecht,et al.  Role of virus strain in conventional and enhanced measles plaque neutralization test. , 1981, Journal of virological methods.

[70]  Global control and regional elimination of measles, 2000–2012. , 2014, Releve epidemiologique hebdomadaire.

[71]  R. Cattaneo,et al.  Measles Virus Glycoprotein Complex Assembly, Receptor Attachment, and Cell Entry , 2009, Current topics in microbiology and immunology.

[72]  K. Nagata,et al.  Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation. , 2003, FEBS letters.

[73]  C. Muller,et al.  Neutralizing B cell response in measles. , 2002, Viral immunology.

[74]  A. Hinman,et al.  Immunity against measles and rubella in Massachusetts schoolchildren. , 1986, Developments in biological standardization.