1887

Abstract

The Thai trial (RV144) indicates that a prime–boost vaccine combination that induces both T-cell and antibody responses may be desirable for an effective HIV vaccine. We have previously shown that immunization with synthetic long peptides (SLP), covering the conserved parts of SIV, induced strong CD4 T-cell and antibody responses, but only modest CD8 T-cell responses. To generate a more balanced CD4/CD8 T-cell and antibody response, this study evaluated a pox-vector prime/SLP boost strategy in rhesus macaques. Priming with a replication-competent NYVAC, encoding HIV-1 clade C , and , induced modest IFNγ T-cell immune responses, predominantly directed against HIV-1 Gag. Booster immunization with SLP, covering the conserved parts of HIV-1 Gag, Pol and Env, resulted in a more than 10-fold increase in IFNγ ELISpot responses in four of six animals, which were predominantly HIV-1 Pol-specific. The animals showed a balanced polyfunctional CD4 and CD8 T-cell response and high Ab titres.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000074
2015-06-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/6/1478.html?itemId=/content/journal/jgv/10.1099/vir.0.000074&mimeType=html&fmt=ahah

References

  1. Drexler I., Staib C., Sutter G. 2004; Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential?. Curr Opin Biotechnol 15:506–512 [View Article][PubMed]
    [Google Scholar]
  2. Franchini G., Gurunathan S., Baglyos L., Plotkin S., Tartaglia J. 2004; Poxvirus-based vaccine candidates for HIV: two decades of experience with special emphasis on canarypox vectors. Expert Rev Vaccines 3:SupplS75–S88 [View Article][PubMed]
    [Google Scholar]
  3. Gómez C. E., Nájera J. L., Krupa M., Perdiguero B., Esteban M. 2011; MVA and NYVAC as vaccines against emergent infectious diseases and cancer. Curr Gene Ther 11:189–217 [View Article][PubMed]
    [Google Scholar]
  4. Haynes B. F., Gilbert P. B., McElrath M. J., Zolla-Pazner S., Tomaras G. D., Alam S. M., Evans D. T., Montefiori D. C., Karnasuta C. et al. 2012; Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 366:1275–1286 [View Article][PubMed]
    [Google Scholar]
  5. Kenter G. G., Welters M. J., Valentijn A. R., Lowik M. J., Berends-van der Meer D. M., Vloon A. P., Essahsah F., Fathers L. M., Offringa R. et al. 2009; Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838–1847 [View Article][PubMed]
    [Google Scholar]
  6. Kibler K. V., Gomez C. E., Perdiguero B., Wong S., Huynh T., Holechek S., Arndt W., Jimenez V., Gonzalez-Sanz R. et al. 2011; Improved NYVAC-based vaccine vectors. PLoS ONE 6:e25674 [View Article][PubMed]
    [Google Scholar]
  7. Koopman G., Mortier D., Hofman S., Mathy N., Koutsoukos M., Ertl P., Overend P., van Wely C., Thomsen L. L. et al. 2008; Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian-human immunodeficiency virus viraemia with protein/DNA combination. J Gen Virol 89:540–553 [View Article][PubMed]
    [Google Scholar]
  8. Koopman G., Beenhakker N., Nieuwenhuis I., Doxiadis G., Mooij P., Drijfhout J. W., Koestler J., Hanke T., Fagrouch Z. et al. 2013; DNA/long peptide vaccination against conserved regions of SIV induces partial protection against SIVmac251 challenge. AIDS 27:2841–2851 [View Article][PubMed]
    [Google Scholar]
  9. Létourneau S., Im E. J., Mashishi T., Brereton C., Bridgeman A., Yang H., Dorrell L., Dong T., Korber B. et al. 2007; Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS ONE 2:e984 [View Article][PubMed]
    [Google Scholar]
  10. Loré K., Betts M. R., Brenchley J. M., Kuruppu J., Khojasteh S., Perfetto S., Roederer M., Seder R. A., Koup R. A. 2003; Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J Immunol 171:4320–4328 [View Article][PubMed]
    [Google Scholar]
  11. Melief C. J., van der Burg S. H. 2008; Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8:351–360 [View Article][PubMed]
    [Google Scholar]
  12. Miles A. P., McClellan H. A., Rausch K. M., Zhu D., Whitmore M. D., Singh S., Martin L. B., Wu Y., Giersing B. K. et al. 2005; Montanide ISA 720 vaccines: quality control of emulsions, stability of formulated antigens, and comparative immunogenicity of vaccine formulations. Vaccine 23:2530–2539 [View Article][PubMed]
    [Google Scholar]
  13. Othoro C., Johnston D., Lee R., Soverow J., Bystryn J. C., Nardin E. 2009; Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun 77:739–748 [View Article][PubMed]
    [Google Scholar]
  14. Paoletti E., Tartaglia J., Taylor J. 1994; Safe and effective poxvirus vectors–NYVAC and ALVAC. Dev Biol Stand 82:65–69[PubMed]
    [Google Scholar]
  15. Perdiguero B., Gómez C. E., Cepeda V., Sánchez-Sampedro L., García-Arriaza J., Mejías-Pérez E., Jiménez V., Sánchez C., Sorzano C. O. et al. 2015; Virological and immunological characterization of novel NYVAC-based HIV/AIDS vaccine candidates expressing clade C trimeric soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as Virus-Like Particles. J Virol 89:970–988 [View Article][PubMed]
    [Google Scholar]
  16. Quakkelaar E. D., Redeker A., Haddad E. K., Harari A., McCaughey S. M., Duhen T., Filali-Mouhim A., Goulet J. P., Loof N. M. et al. 2011; Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. PLoS ONE 6:e16819 [View Article][PubMed]
    [Google Scholar]
  17. Raab D., Graf M., Notka F., Schödl T., Wagner R. 2010; The GeneOptimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization. Syst Synth Biol 4:215–225 [View Article][PubMed]
    [Google Scholar]
  18. Rerks-Ngarm S., Pitisuttithum P., Nitayaphan S., Kaewkungwal J., Chiu J., Paris R., Premsri N., Namwat C., de Souza M. et al. 2009; Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361:2209–2220 [View Article][PubMed]
    [Google Scholar]
  19. Rosario M., Bridgeman A., Quakkelaar E. D., Quigley M. F., Hill B. J., Knudsen M. L., Ammendola V., Ljungberg K., Borthwick N. et al. 2010; Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques. Eur J Immunol 40:1973–1984 [View Article][PubMed]
    [Google Scholar]
  20. Rosario M., Borthwick N., Stewart-Jones G. B., Mbewe-Mvula A., Bridgeman A., Colloca S., Montefiori D., McMichael A. J., Nicosia A. et al. 2012; Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques. AIDS 26:275–284 [View Article][PubMed]
    [Google Scholar]
  21. Walker B. D., Burton D. R. 2008; Toward an AIDS vaccine. Science 320:760–764 [View Article][PubMed]
    [Google Scholar]
  22. Welters M. J., Kenter G. G., de Vos van Steenwijk P. J., Löwik M. J., Berends-van der Meer D. M., Essahsah F., Stynenbosch L. F., Vloon A. P., Ramwadhdoebe T. H. et al. 2010; Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc Natl Acad Sci U S A 107:11895–11899 [View Article][PubMed]
    [Google Scholar]
  23. Zhang H., Hong H., Li D., Ma S., Di Y., Stoten A., Haig N., Di Gleria K., Yu Z. et al. 2009; Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+ and CD4+ T cells. J Biol Chem 284:9184–9191 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000074
Loading
/content/journal/jgv/10.1099/vir.0.000074
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF
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