Both vaccines were immunogenic and well tolerated. Compared with Gardasil, Cervarix induced superior vaccine responses among HIV-infected women, whereas in HIV-infected men the difference in immunogenicity was less pronounced.

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BackgroundMicrobial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV.Methodology/Principal FindingsThis was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals.Conclusions/SignificanceLPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our results suggest that microbial translocation may be associated with innate and adaptive immune dysfunction in untreated HIV infection.

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Abstract. Background: Men and women with HIV infection are at increased risk of developing cancers associated with human papillomavirus (HPV). The two licensed prophylactic HPV vaccines protect against de novo infection with HPV-16 and HPV-18, which cause the majority of HPV-associated cancers. Currently, no vaccine efficacy data are available for persons with HIV infection. Nevertheless, some countries have implemented specific HPV vaccination recommendations for HIV-positive populations. To specifically recommend prophylactic HPV vaccination in people with HIV, the vaccines must be safe and immunogenic in immunosuppressed people at a high risk of HPV infection. This review aims to summarise the current knowledge from published HPV vaccine trials in HIV-infected populations, to compile scheduled and ongoing HPV vaccine trials with HIV-positive study populations and to extrapolate the relevant knowledge about HPV vaccine efficacy in HIV-negative populations to an HIV context. Methods: The databases PubMed, Scopus and ClinicalTrials.gov were searched for peer-reviewed articles and scheduled or ongoing clinical HPV vaccine trials enrolling HIV-positive persons. Results: Current data indicate that prophylactic HPV vaccines are safe and immunogenic in different HIV-positive populations (children, female adolescents, adults). Increased immunogenicity has been reported in persons on antiretroviral therapy compared with antiretroviral-naïve persons, whereas no clear association has been found between CD4+ cell count at immunisation and vaccine response. Several scheduled and ongoing HPV vaccine trials aim to determine vaccine efficacy against disease endpoints in HIV-infected study populations. Conclusion:Prophylactic HPV vaccination appears safe, immunogenic and, by extrapolation, likely to reduce HPVassociated cancer development among persons with HIV infection.

Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.

BackgroundShort dimeric or mulitmeric peptides derived from a highly conserved stretch of amino acids from gammaretroviral envelope proteins has been found to have immunosuppressive properties in vitro. Here we test the hypothesis that such immunosuppressive peptides may serve as immunomodulatory reagents for treatment of inflammatory disorders.ResultsThe anti-inflammatory effect of a synthetic retrovirus-derived immunosuppressive peptide of 17 amino acids was tested in two murine skin inflammation models, a TPA-induced acute toxic contact eczema model and an oxazolone-induced allergic contact dermatitis. Overall, mice (n = 24) treated with a topically applied cream containing the dimeric immunosuppressive peptide exhibited a reduction of 28.8% in ear thickness (range 20.1-42.5), whereas the application of a scrambled peptide dimer or a monomer of the immunosuppressive peptide remained without effect (p = 0.028). Furthermore, ear biopsies from mice treated with the dimeric immunosuppressive peptide showed a significant reduction in mRNA of the pro-inflammatory cytokines TNF-α, IL-17C, and IL-6 as well as the chemokine CXCL2 compared to mice treated with control peptides.ConclusionUsing two murine skin inflammation models, we show that an immunosuppressive retroviral peptide is capable of reducing inflammatory disorders. The results indicate that virus-derived immunosuppressive peptides capable of down-regulating several proinflammatory cytokines may represent a novel class of drugs for the treatment of excess inflammation.