A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity

Abstract

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.

Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study

“…The recombinant proteins were produced and purified from E. coli (Schaffartzik et al, 2010(Schaffartzik et al, , 2011. They were injected either alone or with IC31 ® adjuvant that induces a Th1 type response in mice (Olafsdottir et al, 2012;Pattacini et al, 2012) and in humans when used with Mycobacterium tuberculosis antigens ( van Dissel et al, 2010).…”

Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants

“…In some settings the inclusion of a TLR ligand in the formulation skews the response toward a Th1-type of response or shifts it toward a balanced Th1/Th2 type of response, which may be more desirable than a predominant Th2-biased response such as that elicited by alum alone. The more balanced response afforded by inclusion of TLR ligands may increase the effectiveness of vaccine-induced immune responses against many pathogens, including HIV-1 (Baldwin et al, 2012; Darrah et al, 2007; Lousada-Dietrich et al, 2011; Pattacini et al, 2012). …”

Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects

“…The ICS analysis was performed as previously described. 53,54 The antibodies used for the proliferation analysis consisted of anti-CD4 allophycocyanin (APC) anti-CD3 APC-H7, and anti-CD8 Pacific Blue, and those for ICS were anti-CD3 APC-H7, anti-CD4 BD Horizon V450, anti-CD8 FITC, anti-granzyme B (GrzB) Alexa 700, anti-granzyme A (GrzA) PE, CD107a Alexa 700 (BD Biosciences, Cat# 555349, 560176, 558207, 560345, 555366, 560213, 558904, 561340), and anti-perforin PerCP (Abcam, Cat# ab86319). Both analyses were performed with BD LSRII and FACSDiva TM Software (BD Biosciences), using a positive threshold of >1 % CFSE low for CFSE-proliferation except for ICS studies with threshold of >0 .1% T cells expressing cytotoxin.…”