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Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.

Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.ImportanceAlthough there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.

Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau. Methods: CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage. Results: HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection. Fil: Buggert, Marcus. Karolinska Institutet; Suecia. University of Pennsylvania; Estados Unidos Fil: Frederiksen, Juliet. Technical University of Denmark; Dinamarca Fil: Lund, Ole. Technical University of Denmark; Dinamarca Fil: Betts, Michael R.. University of Pennsylvania; Estados Unidos Fil: Biague, Antonio. National Public Health Laboratory; Guinea Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Tauriainen, Johanna. Karolinska Institutet; Suecia Fil: Norrgren, Hans. Lund University; Suecia Fil: Medstrand, Patrik. Lund University; Suecia Fil: SWEGUB CORE group. No especifica; Fil: Karlsson, Annika C.. Karolinska Institutet; Suecia Fil: Jansson, Marianne. Lund University; Suecia. Karolinska Institutet; Suecia

Norsk fiskerinæring har i dag utfordringer når det gjelder å øke videreforedling av rund fisk. Utvikling av nye produkter vil kunne være viktig med hensyn på å øke økonomisk gevinst og for å skape konkurransefortrinn. SALMA-laks er et nisjeprodukt og består av pre rigor-filetert oppdrettslaks av superior kvalitet. SALMA har lenge vært anerkjent for sin egnethet i retter hvor rå fisk er hovedingrediensen, spesielt i retter som sushi og sashimi. Fordi det i Norge er lange tradisjoner for varmebehandling av laks, er det imidlertid også ønskelig å bestemme hvordan SALMA-laks bør varmebehandles for best mulig å bevare råvarens gode kvalitet. Forsøkene i denne oppgaven har hatt til hensikt å kartlegge om og hvordan den sensoriske profilen i SALMA-laks vil påvirkes ved bruk av ulike kombinasjoner av tid og temperaturtid ved varmebehandling i dampovn. Til den sensoriske vurderingen er et profesjonelt panel ansatt ved Nofima Mat benyttet. Panelet bestod av 9 dommere som tidligere har jobbet med råvarer av samme type i ulike sammenhenger. I forsøksprosessen er også varmegjennomgang i råvaren undersøkt ved å konstruere en matematisk modell. Modellen er vurdert i forhold til evne til å predikere kjernetemperatur, og den er deretter benyttet som hjelpemiddel for å fastsette forsøksparametere for varmebehandling av prøver som inngikk i det sensoriske forsøket. Resultatene fra forsøkene indikerer at ulike kombinasjoner av tid og temperatur vil resultere i ulike sensoriske profiler. De fleste egenskapene det er testet for, viser systematiske resultater i forhold til temperatur og oppholdstid i ovn hvor de mildest og hardest varmebehandlede prøvene viser flest forskjeller. Det er også vist at det er mulig å predikere varmegjennomgang i SALMA-laks ved hjelp av en matematisk modell. One of the main challenges of the Norwegian fish industry today is to increase development of new fish-based products. An increase in production of more raffined fish products would provide a competitive edge and might give increased income for the industry. SALMA-salmon is an example of a Norwegian fish product that has been a success in the Norwegian and foreign markets recent years. This is pre-rigor filleted farmed Atlantic Salmon, and is considered an unique product. SALMA-salmon has experienced great success as an ingredient in typically raw fish dishes such as sashimi and sushi. However traditionally, salmon is often served in a cooked manner, and it is therefore of interest to examine the effect of heat treatment on SALMA-salmon and how to heat treat the fish to maintain the surperiore quality. The trials in question have been conducted to examine the effects of different time and temperature combinations on the sensory profile of SALMA-salmon. A sensory panel consisting of 9 trained pannellists was included to discuss and validate the sensory attributes of cooked salmon. In addition, a mathemathical model for describing heat transfer in the salmon samples during and after heat treatment was constructed. The model was assessed by a serial of heat treatment trials and used to construct trial parameters for the sensory experiments. The results of the trials indicate significant differences between samples heat treated by different time and temperature combinations in respect to sensory attributes. The results also imply that a mathematical approximation and simulation might predict core temperatures of salmon samples during and after heat treatment. One of the main challenges of the Norwegian fish industry today is to increase development of new fish-based products. An increase in production of more raffined fish products would provide a competitive edge and might give increased income for the industry. SALMA-salmon is an example of a Norwegian fish product that has been a success in the Norwegian and foreign markets recent years. This is pre-rigor filleted farmed Atlantic Salmon, and is considered an unique product. SALMA-salmon has experienced great success as an ingredient in typically raw fish dishes such as sashimi and sushi. However traditionally, salmon is often served in a cooked manner, and it is therefore of interest to examine the effect of heat treatment on SALMA-salmon and how to heat treat the fish to maintain the surperiore quality. The trials in question have been conducted to examine the effects of different time and temperature combinations on the sensory profile of SALMA-salmon. A sensory panel consisting of 9 trained pannellists was included to discuss and validate the sensory attributes of cooked salmon. In addition, a simple mathemathical model for describing heat transfer in the raw material during and after heat treatment was constructed. The model was assessed by a serial of heat treatment trials and used to construct trial parameters for the sensory experiments. The results of the trials indicate significant differences between samples heat treated by different time and temperature combinations in respect to sensory attributes. The results also imply that a mathematical approximation and simulation might predict core temperatures of salmon samples during and after heat treatment.