Abstract
Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary “street strain” isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.
Highlights
Approximately 33.4 million individuals live with human immunodeficiency virus type-1 (HIV-1) infection, 22 million of whom reside in Sub-Saharan Africa
In 2008, sub-Saharan Africa accounted for 67% of HIV infections worldwide, 68% of new HIV infections among adults and 91% of new HIV infections among children
A conceivable reason for the observed effect is the presence of unknown agents in the plasma samples causing inhibition of the virus through some unclear mechanisms, notably affecting NG7, NG10, NG12, NG64, NG21 and NG23. the study subjects were assumed to not be on treatment at the time of the acquisition of the plasma, the presence of the high level background against all isolates including amphotropic Murine Leukemia Virus envelope (aMLV) suggest that some may have been. gp160 nucleotide sequences of envelope genes of isolated virions from each 3 individuals with broad crossneutralizing activity and 3 individuals with very low neutralizing antibody activity were sequenced
Summary
Approximately 33.4 million individuals live with human immunodeficiency virus type-1 (HIV-1) infection, 22 million of whom reside in Sub-Saharan Africa. The development of a vaccine to prevent HIV infection is a global health priority. Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine since they were unable to elicit consistent T-cell or protective antibody responses [2,3,4,5,6]. The AIDSVAX B/E rgp120 vaccine used in the RV144 trial in Thailand is considered inappropriate for clinical trials in sub-Sahara Africa where the genetic diversity of group M HIV-1 is highest and where the epidemic is driven by HIV-1 clades different from those found in Thailand as well as to a lesser extent HIV-2 [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
