E Sandström

OA04-02. Strong HIV-specific CD4 and CD8 T-lymphocyte proliferation in HIV-1 DNA prime/modified vaccinia virus Ankara (MVA) heterologous boost vaccinees

Methods Healthy volunteers were immunized intradermally or intramuscularly (with or without adjuvant GM-CSF protein) with DNA expressing HIV-1 gag, env, rev and rt at months 0, 1 and 3 using a Biojector and were boosted at nine months with an MVA expressing heterologous inserts of HIV-1 gag, env and pol genes. Lymphoproliferative responses to AT-2 inactivated HIV-1 antigen were tested by a 3H-thymidine uptake assay and a flow-cytometric assay of specific cell-mediated immune-response in activated whole blood (FASCIA-WB) two weeks after HIV-1 MVA boost (n = 38). A FASCIA using peripheral blood mononuclear cells (FASCIA-PBMC) was also employed during the later part of the study (n = 14).

High prevalence of ECG variations and abnormalities in young and healthy TaMoVac 01 HIV vaccine trial volunteers from Tanzania

Vaccinia immunizations have caused peri-/myocarditis. As a result, volunteers receiving Modified Vaccinia Ankara (MVA) are monitored with ECGs. Early Repolarization Syndrome(ERS) has been reported in 1-2% and Left Ventricular ypertrophy(LVH) in <10% of young, healthy populations across different ethnicities. These changes have been described as normal ECG variations, and according to early reviews, are more frequent in African and Asian populations. A prevalence of 90% has been reported for ST-Elevation in young males in several studies from industrialized and developing countries. ECG was performed in healthy HIV negative volunteers during screening for the Phase II ”TaMoVac01” HIV Vaccine Trial in DarEsSalaam and Mbeya, Tanzania. ECG variations that could potentially interfere with the later interpretation of myocarditis/pericarditis were confirmed by a panel of international cardiologists and led to exclusion from the study. These were ST-segment elevation, T-wave abnormalities, signs of LVH and ERS. 263 Volunteers (mean age 24.4 years, 63.5% males) had a baseline ECG evaluation performed. 19% of ECGs showed ERS, 20.3% showed LVH and 77% showed ST-elevation. 22.1% of volunteers were screened out due to ECG findings, none of whom had a history of cardiac disease, although one participant had a systolic murmur which led to echocardiogram. Dilation of the left ventricle was diagnosed. Although the prevalence of ST elevation was no higher than expected in young males, ERS and LVH was far more common than the literature suggested in this cohort of clinically healthy, young Tanzanians.Exclusions were due to the presence of more than one abnormality. None had symptoms that were clinically relevant, although a significant cardiac finding was revealed through chocardiogram in one participant. The clinical benefit of ECG screening in the context of vaccine studies in healthy volunteers remains to be determined, but it is clear from this study that it added considerably to the number of screenouts.

Breadth, phenotype and functionality of Gag-specific T cell responses induced by a heterologous DNA/MVA prime-boost HIV-1 vaccine regimen

Breadth, phenotype and functionality of Gag-specific T cell responses induced by a heterologous DNA/MVA prime-boost HIV-1 vaccine regimen L Podola, A Bauer, A Haule, L Sudi, C Nilsson, K Godoy-Ramirez, P Mann, M Missanga, B Kaluwa, L Maboko, C Lueer, M Mwakatima, S Aboud, M Bakari, J Currier, M Robb, S McCormack, S Joseph, E Lyamuya, M Hoelscher, B Wahren, E Sandstrom, G Biberfeld, C Geldmacher, A Kroidl

Enrolment and logistical challenges in TaMoVac 01 Phase I/II HIV trial despite the completion of an earlier (HIVIS-03 trial trial) in Dar es Salaam

Background Participation of sub-Saharan countries in HIV vaccine trials is important in the fight against HIV/AIDS, and has to be sustained by continued trials. Experiences from earlier trials are expected to influence the design and the performance of subsequent trials. Following completion of HIVIS-03 trial, TaMoVac01 trial was initiated. We compare enrolment experiences between the two trials.

Preferential targeting of conserved Gag regions after vaccination with a heterologous DNA prime Modified Vaccinia Ankara boost HIV vaccine regime

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P04-16. Orally exposed uninfected individuals have systemic anti-HIV response correlating with partner's viral load

Background We have previously shown that this cohort of exposed uninfected individuals (EU) of men who have sex with men (MSM) display HIV-1 neutralizing capacity in their salivary IgA1 (AIDS 2009). To investigate whether oral HIV-1 exposure mounts also a systemic anti-HIV-1 response, we have here investigated consecutive samples of plasma (unfractioned and IgA1 purified) for neutralizing capacity, and whether the response correlates with exposure measured by viral load in the HIV-positive partners.

HIV-1 Specific CD4 and CD8 T-cell Responses Associated With Low Viral Load in Treatment-Naïve HIV-1 Infected Individuals

In preparation for monitoring of vaccine-induced responses, we determined HIV-specific cell-mediated immune responses in 17 treatment naive HIV-1 infected individuals with > 400 CD4+ T cells/ml for at least 5 years including 9 patients with low viral load (VL, 5000 copies/ml). HIV-1 specific IFN-γ-production and cytolytic activity were higher in subjects with low VL. The differences between the two groups were statistically significant for CD4+ Tcell responses to Gag and Nef peptides, tested by a longterm (48 h) ICS assay and of border-line significance for the Gag-specific cytolytic responses measured by a flowcytometry assay and a chromium release assay. We also found a significant inverse correlation between VL and IFN-γ-production by CD8+ T-cells in response to Gag as measured by ICS. The ELISpot IFN-γ response was not significantly different in patients with high and low VL. During a median follow-up period of 2.4 years, 6 of 8 subjects with high VL and 1 of 9 with low VL showed decreasing CD4+ T-cell counts, and ARV treatment was more frequently initiated in the former patient group (5 of 8 versus 1 of 9). The CD4 and CD8 T cell immune responses found to be associated with low VL and stable CD4 counts may be of importance for protection. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005