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It remains a challenge to develop a successful human immunodeficiency virus (HIV) vaccine that is capable of preventing infection. Here, we utilized the benefits of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs) and B cells, as an adjuvant for our simian immunodeficiency virus (SIV) DNA vaccine in rhesus macaques. We coexpressed the CD40L with our DNA/SIV vaccine such that the CD40L is anchored on the membrane of SIV virus-like particle (VLP). These CD40L containing SIV VLPs showed enhanced activation of DCs in vitro. We then tested the potential of DNA/SIV-CD40L vaccine to adjuvant the DNA prime of a DNA/modified vaccinia virus Ankara (MVA) vaccine in rhesus macaques. Our results demonstrated that the CD40L adjuvant enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV CD8 and CD4 T cell responses, significantly delayed the acquisition of heterologous mucosal SIV infection, and improved viral control. Notably, the CD40L adjuvant enhanced the control of viral replication in the gut at the site of challenge that was associated with lower mucosal CD8 immune activation, one of the strong predictors of disease progression. Collectively, our results highlight the benefits of CD40L adjuvant for enhancing antiviral humoral and cellular immunity, leading to enhanced protection against a pathogenic SIV. A single adjuvant that enhances both humoral and cellular immunity is rare and thus underlines the importance and practicality of CD40L as an adjuvant for vaccines against infectious diseases, including HIV-1. IMPORTANCEDespite many advances in the field of AIDS research, an effective AIDS vaccine that can prevent infection remains elusive. CD40L is a key stimulator of dendritic cells and B cells and can therefore enhance T cell and antibody responses, but its overly potent nature can lead to adverse effects unless used in small doses. In order to modulate local expression of CD40L at relatively lower levels, we expressed CD40L in a membrane-bound form, along with SIV antigens, in a nucleic acid (DNA) vector. We tested the immunogenicity and efficacy of the CD40L-adjuvanted vaccine in macaques using a heterologous mucosal SIV infection. The CD40L-adjuvanted vaccine enhanced the functional quality of anti-Env antibody response and breadth of anti-SIV T cell responses and improved protection. These results demonstrate that VLP-membrane-bound CD40L serves as a novel adjuvant for an HIV vaccine. N ovel vaccine approaches that elicit strong humoral and cellular immunity with high functional quality will aid HIV vaccine development. Here, we utilized the benefits of CD40L, a costimulatory molecule belonging to the tumor necrosis factor superfamily (TNFSF), that can stimulate both dendritic cells (DCs) and B cells for enhancing T cell and antibody (Ab) responses (1). CD40L activates DCs and enhances the priming of the cytotoxic CD8 T cell response (2-4). CD40L also enhances the survival and differentiation of activated B cells, leading to increased germinal c...

FOXP3+CD8+ T cells are present at low levels in humans; however, the function of these cells is not known. In this study, we demonstrate a rapid expansion of CD25+FOXP3+CD8+ regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques. The expansion was pronounced in lymphoid and colorectal mucosal tissues, preferential sites of virus replication. These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro. They also expressed low levels of granzyme B and perforin, suggesting that these cells do not possess killing potential. Expansion of CD8 Tregs correlated directly with acute phase viremia and inversely with the magnitude of antiviral T cell response. Expansion was also observed in HIV-infected humans but not in SIV-infected sooty mangabeys with high viremia, suggesting a direct role for hyperimmune activation and an indirect role for viremia in the induction of these cells. These results suggest an important but previously unappreciated role for CD8 Tregs in suppressing antiviral immunity during immunodeficiency virus infections. These results also suggest that CD8 Tregs expand in pathogenic immunodeficiency virus infections in the nonnatural hosts and that therapeutic strategies that prevent expansion of these cells may enhance control of HIV infection.

Menstrual hygiene management (MHM) has gained some attention and several literature reviews have been published. However, both original papers and reviews tend to focus on absorbent access and use and not on the disposal of menstrual waste. This review aims to fill a gap in the water, sanitation and hygiene (WASH) sector by bringing a focus specifically on menstrual hygiene safe disposal in low- and middle-income countries (LMIC). We reviewed published literature since 2002 on menstrual hygiene with a focus on menstrual waste management and menstrual absorbent disposal in LMIC. Database searches were conducted of both peer reviewed literature and grey literature, in addition to hand searching of references of relevant earlier literature reviews. In total 152 articles and reports were identified and 75 met the inclusion criteria and was included in the final review. Existing polices on MHM was also reviewed with a focus on India and South Africa. The review showed that disposal of menstrual waste is often neglected MHM and sanitation value chains, leading to improper disposal and negative impacts on users, the sanitation systems and the environment. Findings call for further research to gain better understandings of MHM waste streams, disposal behaviors, absorbent materials and waste management technologies to deliver health, safety, mobility and dignity for women and girls.