Abstract
The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa; however, there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants, we have assessed whether the B-cell-activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV-1 gp140. Following intranasal immunisation, TSLP but not APRIL or BAFF induced strong humoral responses both in serum and mucosa. The adjuvant effect of TSLP on humoral responses was similar to that of cholera toxin (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140.
Highlights
The predominant route of sexual HIV transmission to women is via the mucosa of the genitourinary tract
Due to inherent safety issues, cholera toxin (CT), the model mucosal adjuvant used for many animal studies, is not appropriate for human use, and detoxified versions of CT and the closely related heat-labile enterotoxins (LTs) from Escherichia coli have safety concerns for intranasal use in humans [6]
We have investigated whether thymic stromal lymphopoietin (TSLP), a proliferation-inducing ligand (APRIL) and BAFF can be used as effective intranasal adjuvants for HIV-1 gp140
Summary
The predominant route of sexual HIV transmission to women is via the mucosa of the genitourinary tract For this reason, there is a growing consensus that a vaccine is needed that can induce. Nasal immunisation has long been reported as one of the most effective routes to induce immune responses in the female genital tract [3]. Are mucosal responses per se often short-lived, antibody responses to HIV envelope proteins can rapidly wane in the systemic compartment after each immunisation [14,15,16] This only serves to highlight the pressing need to develop novel mucosal adjuvant strategies for HIV-1 envelope based vaccines
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