Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative resistance of human immunodeficiency virus type 1 (HIV-1) primary isolates (PIs) to neutralization by a wide range of antibodies remains a theoretical and practical barrier to the development of an effective HIV vaccine. One model to account for the differential neutralization sensitivity between Pls and laboratory (or T-cell line-adapted [TCLA]) strains of HIV suggests that the envelope protein (Env) complex is made more accessible to antibody binding as a consequence of adaptation to growth in established cell lines. Here, we revisit this question using genetically related PI and TCLA viruses and molecularly cloned env genes. By using complementary techniques of flow cytometry and virion binding assays, we show that monoclonal antibodies targeting the V3 loop, CD4-binding site, CD4-induced determinant of gp120, or the ectodomain of gp41 bind equally well to PI and TCLA Env complexes, despite large differences in neutralization outcome. The data suggest that the differential neutralization sensitivity of PI and TCLA viruses may derive not from differences in the initial antibody binding event but rather from differences in the subsequent functioning of the PI and TCLA Envs during virus entry. An understanding of these as yet undefined differences may enhance our ability to generate broadly neutralizing HIV vaccine immunogens.
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PMID:Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. 1122 97

A vaccine that induces broadly neutralizing antibodies (bnAbs) against the human immunodeficiency virus (HIV) would be instrumental in controlling the disease. The membrane proximal external region (MPER) peptide is an appealing antigen candidate since it is conserved and is the target of several human bnAbs, such as 2F5. We previously found that liposomes containing cobalt porphyrin-phospholipid (CoPoP) can bind to a his-tagged MPER peptide, resulting in biomimetic antigen presentation on a lipid bilayer. The present study generated various his-tagged, synthetic MPER fragments, which were bound to liposomes containing CoPoP and a synthetic monophosphoryl lipid A (MPLA) and assessed for immunogenicity in mice. MPER peptides with amino acids stretches originating from the membrane insertion point that were at least 25 amino acids in length, had greater 2F5 reactivity and induced stronger antibody responses, compared to shorter ones. Immunization with the lipid-presented MPER elicited stronger antibody responses compared to Alum and Montanide adjuvants, which could recognize recombinant gp41 and gp140 proteins that contained MPER sequences. The induced antibodies neutralized a tier 1A virus that is sensitive to neutralizing antibodies (W61D(TCLA)0.71), but not another tier 1A nor a tier 2 strain. Co-formulation of the MPER peptide with an unrelated malaria protein antigen (Pfs25) that is effectively adjuvanted with liposomes containing CoPoP and MPLA resulted in elicitation of higher MPER antibody levels, but did not improve neutralization, possibly due to interference with proper peptide presentation in the membrane. Murine hybridomas were generated that produced MPER antibodies, but they were non-neutralizing. These results do not show that bnAbs could be generated with MPER peptides and CoPoP liposomes, but do not rule out this possibility with additional improvements to the approach.
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PMID:An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice. 3183 30