Comparison of intranasal with targeted lymph node immunization using PR8‐Flu ISCOM adjuvanted HIV antigens in macaques

Abstract

The rapidly spreading HIV epidemic requires a vaccine that elicits potent mucosal immunity to halt or slow transmission. Induction of these responses will depend on the use of appropriate adjuvants and targeting of the mucosal immune system. Previously, immune stimulating complexes (ISCOM) have shown great potency as adjuvant in the induction of mucosal responses in mice and systemic responses in non-human primates. In this study, HIV formulated in PR8-Flu ISCOM adjuvant was applied to immunize rhesus macaques against HIV; targeting the mucosa either via intranasal (IN) application or via targeted lymph node immunization (TLNI). While, strong systemic, HIV specific, cytokine, lymphoproliferative, and antibody responses were induced via the TLNI route, the IN application generated only low responses. Furthermore, all four animals immunized via TLNI developed vaginal IgA antibodies against gp120. In conclusion, in contrast to what has been demonstrated in mice, the IN application of PR8-Flu ISCOM did not induce strong immune responses in rhesus macaques unlike those immunized by the TLNI route.

Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

“…These results are in line with already published data showing enhanced immunogenicity of intralymphatic injection using plasmid DNA vaccines [17], major histocompatibility complex class I binding peptides [18] and tumour cells [28]. Other groups have also demonstrated enhanced efficacy by targeted lymph node immunisation with immunostimulatory complexes [30], bacteriophages [31], a recombinant simian immunodeficiency virus vaccine [32], and a canary pox virus-based cancer vaccine [33]. In addition, intralymphatic administration required less than 1% antigen [17] or immune stimulatory molecules [34] to induce potent cytotoxic T-cell immune responses than did subcutaneous antigen administration.…”

Immunogenicity of HIV Virus-Like Particles in Rhesus Macaques by Intranasal Administration

“…administration. Such results have been obtained using different vaccine delivery systems, which suggests that they are not vaccine related (3,24,26,27).…”

“…In addition to adjuvants, particulate antigens (e.g., virus-like particles [VLPs]) have been shown to be advantageous for intranasal immunization, given that they efficiently target antigen-presenting cells (APCs) and facilitate the induction of potent immune responses (7,9,10,11,16,18,31,34,41,43,44). However, several vaccine concepts have been evaluated in nonhuman primates (NHPs) by intranasal administration with inconsistent immunogenicity results, probably related to the different vaccination strategy (3,17,24,26,27,29).…”

“Wrapped Up” Vaccines in the Context of HIV-1 Immunotherapy

“…In contrast, intranasal application resulted in very weak responses. Currently, ISCOM-based vaccines have been approved for veterinary use and are undergoing clinical trials for human use [295].…”