Chimeric Rhinoviruses Displaying MPER Epitopes Elicit Anti-HIV Neutralizing Responses

Background: The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV. Methodology/Principle Findings: Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPERdisplaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested. Conclusions: Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection

Citrus sinensis mRNA for putative ribosomal protein L35 (rpl35 gene).

Sequenza isolata e depositata, previa accettazione, in banca dati (NCBI GenBank Data Base

Citrus sinensis partial mRNA for hypothetical protein (GI:56409877)

Sequenza isolata e depositata, previa accettazione, in banca dati (NCBI GenBank Data Base

Rhizoctonia fragariae partial mRNA for putative reduced viability upon starvation protein 161 (rvs161 gene)

Sequenza isolata e depositata, previa accettazione, in banca dati (NCBI GenBank Data Base

Fragaria vesca mRNA for hypothetical protein (GI:55724901).

Sequenza isolata e depositata, previa accettazione, in banca dati (NCBI GenBank Data Base