Abstract
HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells, and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.
Highlights
Semen is a complex fluid composed of a cellular fraction containing spermatozoa and leukocytes, and a non-cellular fraction, the so-called seminal plasma (SP) including diverse set of components such as cytokines, chemokines, fibrils, immunoglobulins, complement factors, and bacteria [1,2,3]
Two groups of six cynomolgus macaques immunized by subcutaneous injection of 4 × 108 plaque-forming units (PFU) of rMVA-HIV-1 at weeks 0 and 8, were exposed to PBS, as controls, or to a SP pool at days 70, 72, 74, and 76 following first vaccine injection
These results suggest that SP exposures do not significantly modify the vaccine-specific humoral responses
Summary
Semen is a complex fluid composed of a cellular fraction containing spermatozoa and leukocytes, and a non-cellular fraction, the so-called seminal plasma (SP) including diverse set of components such as cytokines, chemokines, fibrils, immunoglobulins, complement factors, and bacteria [1,2,3]. Seminal Plasma and Vaccine Responses modifications [4], such as the induction of pro-inflammatory cytokine/chemokine production [5, 6], and upregulation of inflammatory upstream regulator expression, such as Cyclooxygenase-2 (COX-2) [7], and leukocyte infiltration [8, 9]. These modifications of the local environment have been described to promote fertility and are not due to intercourse itself, but require SP exposure [10], as described in vitro and in vivo in mice [5] and pigs [11] as well as humans [10]. The effect of HIV-1+ SP on the local environment of the FRT is still uncharacterized
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