Occurrence of Escape Favoring Mutations in The Targets of 2F5 and 4E10 Antibodies of HIVgp41 : A Metadata Analysis
The preventive vaccine for HIV has been an unachieved goal and the increasing prevalence burdens the field of medicine for the last three decades. The challenge is due to the substantial overall sequence variability that is found across the genome of HIV- 1. Here a retrospection has been done to investigate the degree of conservation in the targets of the 2F5 and 4E10 neutralizing antibodies. The 6 and 7 amino acid long epitopes of the neutralizing antibodies are embedded in the MPER (Membrane Proximal External Region) of the HIV-1 glycoprotein 41.
HIV-1 gp 41 nucleotide sequences reported from different parts of the world were collected as fasta sequences on a random basis. The sequences were aligned and investigated for mutations found in the epitopes targeted by the 2F5 and 4E10 neutralizing antibodies.
Substitutions and deletions almost in all the residues were found. The mutations that were found in each of the residue can critically affect the affinity of the neutralizing antibodies. The occurrence of these mutations in the critical residues in combination with the neighboring residues may offer a survival advantage for the virus to escape from these circulating neutralizing antibodies. This invariant nature which is substantiated earlier has been diverging over the years.
The mutations can crucially alter the dynamicity and the reactivity of the 2F5 and 4E10 antibodies directed to the putative vaccine targets. This confers the fact that these targets may be less appropriate a candidate for a vaccine. The infidel reverse transcriptase that copies these ‘selfish’ survivable mutants is characteristically favoring the virus to make progeny which can escape the surveillance by these neutralizing antibodies. Hence, due to the observed trend in the lack of conservation, it becomes necessary to search for better candidates for a stronger immune response that promises success in vaccine strategies.