Different immune response of mice immunized with conjugates containing multiple copies of either consensus or mixotope versions of the V3 loop peptide from human immunodeficiency virus type 1.
The critical role that antibody responses to the V3 loop epitope play in human immunodeficiency virus type 1 (HIV-1) neutralization has caused this peptide to be used in many HIV-1 vaccine candidates. To enhance cross-reactivity toward several V3 sequences, a database of 50 peptides of the V3 region from HIV-1 subtype A was used to design both a consensus peptide and a combinatorial peptide (mixotope) library representative of these sequences. The two immunogens (consensus and mixotope) were incorporated into multiple antigen peptide (MAP) constructions, conjugated to a recombinant surface antigen from hepatitis B virus (HbsAg) carrier protein, and inoculated to mice in combination with a C4 (CD4-binding) peptide MAP construction, also conjugated to HBsAg. The respective responses and cross-reactivity to several V3 loop sequences of both types of immunogens were compared. Mice inoculated with the V3 consensus-MAP-HBsAg + C4-MAP-HBsAg mixture elicited higher antibody responses than those given the V3 mixotope-MAP-HBsAg + C4-MAP-HBsAg mixture. In addition, pooled serum from the first group of immunogens analyzed at dilution 1:100 had higher cross-reactivity against V3 peptides on cellulose membranes than those from mice given the combinatorial immunogen. Fine epitope mapping of both consensus and C4 peptide by the spot synthesis technique showed that sera of the first group strongly recognized both sequences in their entirety, whereas mice immunized with the mixotope library recognized only the N-terminal region of V3. These results seem to suggest that the V3 consensus peptide is superior to the combinatorial strategy in inducing potent and cross-reactive responses to HIV.
Cruz
Luis J
LJ
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona-Universitat de Barcelona, Josep Samitier 1, E-08028 Barcelona, Spain.
Iglesias
Enrique
E
Aguilar
Julio C
JC
Cabrales
Ania
A
Reyes
Osvaldo
O
Andreu
David
D
D000595:Amino Acid Sequence; D000818:Animals; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D003429:Cross Reactions; D018604:Epitope Mapping / Q000379:methods; D005260:Female; D018628:Gene Dosage; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007106:Immune Sera; D010446:Peptide Fragments; D022223:Vaccines, Subunit