Boosting of ALVAC-SIV vaccine-primed macaques with the CD4-SIVgp120 fusion protein elicits antibodies to V2 associated with a decreased risk of SIVmac251 acquisition

The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hypothesized that the breadth and functional profile of Abs induced by an ALVAC/envelope protein regimen could be improved by substituting the monomeric gp120 boost, with the full-length single-chain (FLSC) protein. FLSC is a CD4-gp120 fusion immunogen that exposes cryptic gp120 epitopes to the immune system. We compared the immunogenicity and relative efficiency of an ALVAC-SIV vaccine boosted either with bivalent FLSC proteins or with monomeric gp120 in alum. FLSC was superior to monomeric gp120 in directing Abs to the C3 a2 helix, the V5 loop, and the V3 region that contains the putative CCR5 binding site. In addition, FLSC boosting elicited significantly higher binding Abs to V2 and increased both the Ab-dependent cellular cytotoxicity activity and the breadth of neutralizing Abs. However, the FLSC vaccine regimen demonstrated only a trend in vaccine efficacy, whereas the monomeric gp120 regimen significantly decreased the risk of SIVmac251 acquisition. In both vaccine regimens, anti-V2 Abs correlated with a decreased risk of virus acquisition but differed with regard to systemic or mucosal origin. In the FLSC regimen, serum Abs to V2 correlated, whereas in the monomeric gp120 regimen, V2 Abs in rectal secretions, the site of viral challenge, were associated with efficacy. The Journal of Immunology, 2016, 197: 2726-2737

Recent applications of microwave assisted cyclizations promoted by polyphosphoric acid esters to the synthesis of nitrogen heterocycles

Polyphosphoric acid (PPA) esters PPE (ethyl polyphosphate) and PPSE (trimethylsilyl polyphosphate) are mild reagents of the Lewis acid type with a high dehydrating power due to their ability to react irreversibly with water.They are used mainly to conduct condensation reactions in which they bond to the oxygen atom present in alcohols, carbonyls and carboxylic acid derivatives generating electrophilic carbon species.The introduction describes the preparation, structure and applications of PPE and PPSE in the construction of heterocyclic moieties by both C-C and C-heteroatom bond formation. The main body of this chapter is devoted to the applications of the reagents to the synthesis of nitrogen heterocycles under microwave irradiation developed by our group.Fil: Orelli, Liliana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Bisceglia, Juan Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Gruber, Nadia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Díaz, Jimena Estela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Mollo, María Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentin

Promises and limitations of murine models in the development of anticancer T-cell vaccines

Murine models have been instrumental in defining the basic mechanisms of antitumor immunity. Most of these mechanisms have since been shown to operate in humans as well. Based on these similarities, active vaccination strategies aimed at eliciting antitumor T-cell responses have been elaborated and successfully implemented in various mouse models. However, the results of human antitumor vaccination trials have been rather disappointing thus far. This review summarizes the different experimental approaches used in mice to induce antitumor T-cell responses and identifies some critical parameters that should be considered when evaluating results from murine models