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9 participants - HIV-negative IDUs

The frequency of HIV-1 specific cellular immune responses in seronegative individuals with parenteral and/or heterosexual HIV-1 exposure . B.V. Murashev, O.V. Nazarenko, E.B. Akulova , A.K. Artemyeva, S.V. Verevochkin, O.V. Toussova, A.P.Kozlov. The Biomedical Center, St. Petersburg, Russia.

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9 participants - HIV-negative IDUs

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  1. The frequency of HIV-1 specific cellular immune responses in seronegative individuals with parenteral and/or heterosexual HIV-1 exposure. B.V. Murashev, O.V. Nazarenko, E.B. Akulova, A.K. Artemyeva, S.V. Verevochkin, O.V. Toussova, A.P.Kozlov. The Biomedical Center, St. Petersburg, Russia.

  2. Examine Group 9 participants -HIV-negativeIDUs 10 participants -HIV-negative individuals living with HIV-positive partners (2individuals also had parenteral exposure) 9participants- HIV-positiveindividuals (1 IDUand 8 HIV-positive partners from discordant couples) HIV status of the individuals was determined using ELISA, Western Blot and HIV RNA RT-PCR tests.

  3. Examine Group * the number of the unprotected sexual contacts with HIV-positive partner within a year ** (+) joint use of the injection instrumentation within three months

  4. Research plan Blood PBMC Ficoll-purification and cryopreservation N2-freezer 1. IFN-ELISPOT 2. ICS - IFN/TNF/IL-2/CD3/CD4&8 flow cytometry BC EPICS XL Control K- Nef-pool Gag-pool RT-pool Env-pool CEF-pool PHA IFN CD3-CD4- CD3+CD4+ CD3+CD4- TNF IL-2

  5. IFN-ELISPOT and CCRV-genotyping Results * (+) р<0.05 Mann-Whitney U-test; (-) р0.05 Mann-Whitney U-test; (n/a) not analyzed;

  6. IFN-ELISPOT Results p=0.09 * * SFU/106 PBMC * * p=0.3 * * р<0.05 Mann-Whitney U-test between examine group and negative control

  7. - participants included in ICS-study ICS Examine Group

  8. ICS Results: Single cytokine production (n/a) not analysis,

  9. ICS Results: Single cytokine production CD3+CD8+ CD3+CD4+ Nef-pool Nef-pool * * * * % CD3+CD8+ % CD3+CD4+ * * Gag-pool Gag-pool * * % CD3+CD8+ % CD3+CD4+ * * * - Average in group, - Average negative control, * р<0.05 Mann-Whitney U-test between examine group and negative control

  10. ICS Results: T-cell multifunctional responses CD3+CD8+ CD3+CD4+ Nef-pool Gag-pool Nef-pool Gag-pool ESN HIV+

  11. Do observed cellular responses have any protective role against HIV?

  12. All HIV-negative participants had high risk of infection • 89% HIV-negative study subjects had strong Nef peptide pool specific cellular immune responses, 21% subjects responded against Gag peptide pool in IFN-ELISPOT • the majority of seronegative patients were found to be wild type for CCR5-Δ32 (only two were heterozygous) • The multiple HIV-specific cytokine production in both CD4+ and CD8+ T-cells was shown for several subjects • T-cellular immune response is induced to the antigens presented in the complex with HLA on the cell surface • HIV-1 Nefprotein is expressed in latent phase of the infection cycle from the fully spliced viral RNA, and it almost lacks in viral particles

  13. Summary • EitherHIV-negative participants were infected and they demonstrate protective immune response at least to the infection virus • Either there is an alternative (not HIV-1) pathogen whose immunological determinates overlap with HIV-1 proteins (Nef, Gag, RT) • In both cases observed cellular responses may be protective at least against some HIV variants

  14. Summary • If the T-cellular immune response observed in HIV-negative individuals is protective, than • it can work as a barrier for viruses, so it is possible to provide an explanation for: • the genetic bottleneck effect observed for parenteral route of HIV transmission (Masharsky, 2010) • the low genetic diversity (3-7%) of the HIV-1 circulating in the Former Soviet Union countries (Nabatov, 2007) • We could define concretely the immunological properties of the vaccine against HIV. • If the observed immune response is induced by an alternative (not HIV) pathogen, than the discovery of this pathogen may play the key role in HIV/AIDS preventive strategy.

  15. Collaborators: IDU Cohort Studies Biomedical center (St.Petersburg, Russia) Shaboltas A., Toussova O., Skochilov R. HIV-1 status testingBiomedical center (St.Petersburg, Russia) Verevochkin S, Masharsky A., Shevchenko A. CCRV 32 genotype testingBiomedical center (St.Petersburg, Russia) Artemyeva A. Immunological groupBiomedical center (St.Petersburg, Russia) Murashev B., Nazarenko O., Akulova E., Kukhareva P. Dr. A.P. Kozlov - The Biomedical Center and St. Petersburg University St. Petersburg, Russia

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