1887

Abstract

Monitoring serum antibodies against natural infections or after immunizations has been a standard clinical diagnostic procedure. However, collecting blood samples requires trained personnel, and may cause discomfort and increase the risk of complications. In this study, we investigated whether tear samples could serve as a surrogate for serum samples to measure specific antibodies. A widely used preclinical cottontail rabbit papillomavirus (CRPV)/rabbit model has been a surrogate model for high-risk human papillomavirus (HPV) infections. New Zealand white rabbits, either naturally infected with CRPV or immunized with two clinically available HPV vaccines (Gardasil and Cervarix), were examined for antibody generation in both tear and serum samples. We demonstrated that antibodies were detectable in tears from both naturally infected as well as vaccinated animals. Overall, the antibody levels in tears were ~10-fold lower than those from the corresponding serum samples, but background noise was lower in tear samples. The isotypes of antibodies in tears were predominantly IgA and IgG. These findings showed clearly that tears could be a surrogate for serum samples for monitoring antibody responses. As collecting tears causes no discomfort and poses no risk to patients, it represents a novel and promising method for monitoring future HPV epidemiological studies as well as for use in clinical practice.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.064154-0
2014-09-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/9/2030.html?itemId=/content/journal/jgv/10.1099/vir.0.064154-0&mimeType=html&fmt=ahah

References

  1. Allansmith M. 1973; Immunology of the tears. Int Ophthalmol Clin 13:47–72 [View Article][PubMed]
    [Google Scholar]
  2. Buck C. B., Pastrana D. V., Lowy D. R., Schiller J. T. 2005; Generation of HPV pseudovirions using transfection and their use in neutralization assays. Methods Mol Med 119:445–462[PubMed]
    [Google Scholar]
  3. Christensen N. D., Kreider J. W., Cladel N. M., Galloway D. A. 1990; Immunological cross-reactivity to laboratory-produced HPV-11 virions of polysera raised against bacterially derived fusion proteins and synthetic peptides of HPV-6b and HPV-16 capsid proteins. Virology 175:1–9 [View Article][PubMed]
    [Google Scholar]
  4. Cladel N. M., Hu J., Balogh K., Mejia A., Christensen N. D. 2008; Wounding prior to challenge substantially improves infectivity of cottontail rabbit papillomavirus and allows for standardization of infection. J Virol Methods 148:34–39 [View Article][PubMed]
    [Google Scholar]
  5. Coyle P. K., Sibony P. A. 1986; Tear immunoglobulins measured by ELISA. Invest Ophthalmol Vis Sci 27:622–625[PubMed]
    [Google Scholar]
  6. Coyle P. K., Sibony P. A. 1988; Viral antibodies in normal tears. Invest Ophthalmol Vis Sci 29:1552–1558[PubMed]
    [Google Scholar]
  7. Douglas R. G. Jr, Rossen R. D., Butler W. T., Couch R. B. 1967; Rhinovirus neutralizing antibody in tears, parotid saliva, nasal secretions and serum. J Immunol 99:297–303[PubMed]
    [Google Scholar]
  8. Einstein M. H., Baron M., Levin M. J., Chatterjee A., Edwards R. P., Zepp F., Carletti I., Dessy F. J., Trofa A. F. other authors 2009; Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccin 5:705–719 [View Article][PubMed]
    [Google Scholar]
  9. Fox P. D., Khaw P. T., McBride B. W., McGill J. I., Ward K. A. 1986; Tear and serum antibody levels in ocular herpetic infection: diagnostic precision of secretory IgA. Br J Ophthalmol 70:584–588 [View Article][PubMed]
    [Google Scholar]
  10. Friedman M. G. 1990; Antibodies in human tears during and after infection. Surv Ophthalmol 35:151–157 [View Article][PubMed]
    [Google Scholar]
  11. Friedman M. G., Phillip M., Dagan R. 1989; Virus-specific IgA in serum, saliva, and tears of children with measles. Clin Exp Immunol 75:58–63[PubMed]
    [Google Scholar]
  12. Giroglou T., Sapp M., Lane C., Fligge C., Christensen N. D., Streeck R. E., Rose R. C. 2001; Immunological analyses of human papillomavirus capsids. Vaccine 19:1783–1793 [View Article][PubMed]
    [Google Scholar]
  13. Hu J., Budgeon L. R., Cladel N. M., Culp T. D., Balogh K. K., Christensen N. D. 2007a; Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus. J Gen Virol 88:3286–3293 [View Article][PubMed]
    [Google Scholar]
  14. Hu J., Cladel N. M., Balogh K., Budgeon L., Christensen N. D. 2007b; Impact of genetic changes to the CRPV genome and their application to the study of pathogenesis in vivo . Virology 358:384–390 [View Article][PubMed]
    [Google Scholar]
  15. Langford M. P., Orillac R., Chen D., Texada D. 2003; Systemic and ocular antibody responses to inactivated acute hemorrhagic conjunctivitis (AHC) virus; enterovirus 70 (EV70). Ocul Immunol Inflamm 11:197–209 [View Article][PubMed]
    [Google Scholar]
  16. Liotet S., Hartmann C., Batellier L., Chaumeil C., Frottier J. 1987; Anti-HIV-antibodies in tears of patients with AIDS. Fortschr Ophthalmol 84:340–341[PubMed]
    [Google Scholar]
  17. Little J. M., Centifanto Y. M., Kaufman H. E. 1969; Immunoglobulins in human tears. Am J Ophthalmol 68:898–905[PubMed] [CrossRef]
    [Google Scholar]
  18. Madar R., Straka S., Baska T. 2002; Detection of antibodies in saliva – an effective auxiliary method in surveillance of infectious diseases. Bratisl Lek Listy (Tlacene Vyd) 103:38–41[PubMed]
    [Google Scholar]
  19. McCormack P. L., Joura E. A. 2011; Spotlight on quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine(Gardasil®) in the prevention of premalignant genital lesions, genital cancer, and genital warts in women. BioDrugs 25:339–343 [View Article][PubMed]
    [Google Scholar]
  20. Mejia A. F., Culp T. D., Cladel N. M., Balogh K. K., Budgeon L. R., Buck C. B., Christensen N. D. 2006; Preclinical model to test human papillomavirus virus (HPV) capsid vaccines in vivo using infectious HPV/cottontail rabbit papillomavirus chimeric papillomavirus particles. J Virol 80:12393–12397 [View Article][PubMed]
    [Google Scholar]
  21. Nesburn A. B. 1980; Common viral eye diseases and latent infections. Ophthalmology 87:1202–1207 [View Article][PubMed]
    [Google Scholar]
  22. Pastrana D. V., Buck C. B., Pang Y. Y., Thompson C. D., Castle P. E., FitzGerald P. C., Krüger Kjaer S., Lowy D. R., Schiller J. T. 2004; Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18. Virology 321:205–216 [View Article][PubMed]
    [Google Scholar]
  23. Pastrana D. V., Gambhira R., Buck C. B., Pang Y. Y., Thompson C. D., Culp T. D., Christensen N. D., Lowy D. R., Schiller J. T., Roden R. B. 2005; Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2. Virology 337:365–372 [View Article][PubMed]
    [Google Scholar]
  24. Rozanova E. B., Teplinskaia L. E., Kaliberdina A. F., Barisani-Asenbauer T. 2006; Cytomegalovirus antibodies in tear fluid of patients with retinitis. Arch Virol 151:2407–2417 [View Article][PubMed]
    [Google Scholar]
  25. Välimaa H., Tenovuo J., Waris M., Hukkanen V. 2009; Human lactoferrin but not lysozyme neutralizes HSV-1 and inhibits HSV-1 replication and cell-to-cell spread. Virol J 6:53 [View Article][PubMed]
    [Google Scholar]
  26. Van Haeringen N. J. 1981; Clinical biochemistry of tears. Surv Ophthalmol 26:84–96 [View Article][PubMed]
    [Google Scholar]
  27. Villa L. L., Costa R. L., Petta C. A., Andrade R. P., Ault K. A., Giuliano A. R., Wheeler C. M., Koutsky L. A., Malm C. other authors 2005; Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6:271–278 [View Article][PubMed]
    [Google Scholar]
  28. Yan Q., Peng B., Su G., Cohan B. E., Major T. C., Meyerhoff M. E. 2011; Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration. Anal Chem 83:8341–8346 [View Article][PubMed]
    [Google Scholar]
  29. Zhou L., Beuerman R. W. 2012; Tear analysis in ocular surface diseases. Prog Retin Eye Res 31:527–550 [View Article][PubMed]
    [Google Scholar]
  30. Zhou L., Zhao S. Z., Koh S. K., Chen L., Vaz C., Tanavde V., Li X. R., Beuerman R. W. 2012; In-depth analysis of the human tear proteome. J Proteomics 75:3877–3885 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.064154-0
Loading
/content/journal/jgv/10.1099/vir.0.064154-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error