Although this correlation is not a proof of the neutralizing efficiency of CD4i antibodies, it shows that the presence of these MAbs is fully related to the CD4- bound conformation of HIV-1 envelope in vivo. Besides, recent approach towards constraining ��gp120 core�� protein by sitedirected disulfide linkage has been a novel step towards eliciting epitope-specific response against the co-receptor binding site. These vaccination studies indicate the potential importance of strategies directed to raising antibodies against the CD4i site. Some success in protection against HIV-1 acquisition has been afforded by active prophylactic vaccination using either DNA prime-recombinant Env protein boost or viral vector prime-recombinant Env protein boost or adjuvanted recombinant Env proteins in studies performed in nonhuman primate models, and most recently, in humans using a Canarypox vector prime plus recombinant Env protein boost approach in the RV144 Phase III trial performed in Thailand. Recent correlates of risk assessments of the RV144 trial indicated that V1V2-directed IgG antibodies in sera from vaccinees were associated with vaccine-elicited protection. Despite this early ����hypothesis generating���� finding in this first promising HIV-1 vaccine trial, the importance of the diversity of antibodies elicited by other epitopes on Env such as the CD4i epitope, during infection and vaccination, and their role in immune protection against HIV-1 infection warrant further investigation. The present work provides a powerful next generation approach using a novel and stable cross-linked complex of oligomeric gp140 glycoprotein and a CD4 mimetic miniprotein, in order to elicit broadly reactive functional antibody responses targeted to the highly conserved co-receptor binding site of the HIV-1 Env. Moreover, it does so while avoiding the elicitation of undesirable anti-CD4 reactivity. This cross-linked gp140-miniCD4 complex is suitably stable for future vaccine studies in ABT-263 923564-51-6 non-human primate models, and represents a viable Wortmannin PI3K inhibitor strategy for further evaluations of the role of CD4i epitope-directed antibody responses in protection against HIV-1 infection during vaccination. Improving agricultural productivity is essential for maintaining global development and necessary in order to permit future population growth. Historical increases in plant productivity achieved through irrigation, fertilizer application, hybrid selection or genetic modification can be largely attributed to a crops ability to maximize photosynthetic capture. Differences in chlorophyll content and/or chloroplast number are typically directly related to agricultural productivity, with greener plants having increased nitrogen use efficiency, biomass and yield. Plastids, including chloroplasts, are determined early in the plant meristem and further differentiation occurs according to the type of cell in which they will ultimately reside.