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Identification of immunodominant CD4-restricted epitopes co-located with antibody binding sites in individuals vaccinated with ALVAC-HIV and AIDSVAX B/E.

Ratto-Kim S, de Souza MS, Currier JR, Karasavvas N, Sidney J, Rolland M, Valencia-Micolta A, Madnote S, Sette A, Nitayaphan S, Pitisuttuthum P, Kaewkungwal J, Rerks-Ngarm S, O'Connell R, Michael N, Robb ML, Marovich M, Kim JH - PLoS ONE (2015)

Bottom Line: Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction.Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181).There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States of America.

ABSTRACT
We performed fine epitope mapping of the CD4+ responses in the ALVAC-HIV-AIDSVAX B/E prime-boost regimen in the Thai Phase III trial (RV144). Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction. Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181). There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

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Related in: MedlinePlus

Peptide 32 is shown in comparison to other synthesized peptides containing sieve mutations at position 181 and other mutations (at positions 183–185) that were observed in the viruses found in vaccinee breakthrough infections.The heat map on the right represents the IFN-γ fold reduction response of the 4 gp120A244 specific CD4+ T cell lines to the altered peptides relative to the consensus sequence. The aa mutation P183Q, was similarly expressed between the the two arms with breakthrough HIV infections. In particular, in the 44 vaccinees, 16 were P (36%), 22 Q (50%), and 5 other residues (E,K,N,S) were also most common. For the 66 Placebo recipients, 28 were P (42%), 31Q (47%), and 7 were other residues (E,K,R,S).
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pone.0115582.g003: Peptide 32 is shown in comparison to other synthesized peptides containing sieve mutations at position 181 and other mutations (at positions 183–185) that were observed in the viruses found in vaccinee breakthrough infections.The heat map on the right represents the IFN-γ fold reduction response of the 4 gp120A244 specific CD4+ T cell lines to the altered peptides relative to the consensus sequence. The aa mutation P183Q, was similarly expressed between the the two arms with breakthrough HIV infections. In particular, in the 44 vaccinees, 16 were P (36%), 22 Q (50%), and 5 other residues (E,K,N,S) were also most common. For the 66 Placebo recipients, 28 were P (42%), 31Q (47%), and 7 were other residues (E,K,R,S).

Mentions: In an attempt to understand if this mutation had any effect on the CD4+ recognition of the epitope a series of peptides were synthesized that contained the aa mutation at position 181 (I to L mutation) and other mutations that although not significantly associated with the vaccine treatment, were also common in the HIV sequences from the breakthrough infections in RV144. The peptide that contained the I181L mutation on its own was recognized in an ICS assay as well as the original peptide (Fig. 3 and S3 Table). The aa mutation P183Q, that abolished peptide recognition was not differentially expressed between vaccine and placebo breakthrough viruses.


Identification of immunodominant CD4-restricted epitopes co-located with antibody binding sites in individuals vaccinated with ALVAC-HIV and AIDSVAX B/E.

Ratto-Kim S, de Souza MS, Currier JR, Karasavvas N, Sidney J, Rolland M, Valencia-Micolta A, Madnote S, Sette A, Nitayaphan S, Pitisuttuthum P, Kaewkungwal J, Rerks-Ngarm S, O'Connell R, Michael N, Robb ML, Marovich M, Kim JH - PLoS ONE (2015)

Peptide 32 is shown in comparison to other synthesized peptides containing sieve mutations at position 181 and other mutations (at positions 183–185) that were observed in the viruses found in vaccinee breakthrough infections.The heat map on the right represents the IFN-γ fold reduction response of the 4 gp120A244 specific CD4+ T cell lines to the altered peptides relative to the consensus sequence. The aa mutation P183Q, was similarly expressed between the the two arms with breakthrough HIV infections. In particular, in the 44 vaccinees, 16 were P (36%), 22 Q (50%), and 5 other residues (E,K,N,S) were also most common. For the 66 Placebo recipients, 28 were P (42%), 31Q (47%), and 7 were other residues (E,K,R,S).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321833&req=5

pone.0115582.g003: Peptide 32 is shown in comparison to other synthesized peptides containing sieve mutations at position 181 and other mutations (at positions 183–185) that were observed in the viruses found in vaccinee breakthrough infections.The heat map on the right represents the IFN-γ fold reduction response of the 4 gp120A244 specific CD4+ T cell lines to the altered peptides relative to the consensus sequence. The aa mutation P183Q, was similarly expressed between the the two arms with breakthrough HIV infections. In particular, in the 44 vaccinees, 16 were P (36%), 22 Q (50%), and 5 other residues (E,K,N,S) were also most common. For the 66 Placebo recipients, 28 were P (42%), 31Q (47%), and 7 were other residues (E,K,R,S).
Mentions: In an attempt to understand if this mutation had any effect on the CD4+ recognition of the epitope a series of peptides were synthesized that contained the aa mutation at position 181 (I to L mutation) and other mutations that although not significantly associated with the vaccine treatment, were also common in the HIV sequences from the breakthrough infections in RV144. The peptide that contained the I181L mutation on its own was recognized in an ICS assay as well as the original peptide (Fig. 3 and S3 Table). The aa mutation P183Q, that abolished peptide recognition was not differentially expressed between vaccine and placebo breakthrough viruses.

Bottom Line: Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction.Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181).There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States of America.

ABSTRACT
We performed fine epitope mapping of the CD4+ responses in the ALVAC-HIV-AIDSVAX B/E prime-boost regimen in the Thai Phase III trial (RV144). Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction. Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the α4β7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181). There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.

Show MeSH
Related in: MedlinePlus