Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

Mohamed, Y. A.; Borthwick, Nicola; Moyo, Nathifa; Murakoshi, Hayato; Akahoshi, Tomohiro; Siliquini, Francesca; Hannoun, Zara; Crook, Alison; Hayes, Peter; Fast, Patricia E.; Mutua, Gaudensia; Jaoko, Walter; Silva-Arrieta, Sandra; Llano, Anuska; Berthou, Christian; Takiguchi, Masafumi; Hanke, Tomáš

doi:10.3390/vaccines8020260

Cited by 7 publications

(4 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The immune responses directed towards epitopes in conserved regions are usually subdominant but may provide protection against multiple HIV-1 subtypes [ 17 , 53 ]. Many studies that included Pol epitopes in vaccine candidates showed stimulation of effective CTL responses [ 18 , 56 , 61 , 62 ]. Ahmed et al, showed control of HIV-1 replication in vitro through stimulation of Pol CTL responses by a vaccine that contained subdominant epitopes [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Nkone

Loubser

Quinn

et al. 2022

Virol J

View full text Add to dashboard Cite

Background Despite multiple attempts, there is still no effective HIV-1 vaccine available. The HIV-1 polymerase (pol) gene is highly conserved and encodes cytotoxic T-lymphocyte (CTL) epitopes. The aim of the study was to characterise HIV-1 Pol CTL epitopes in mostly sample pairs obtained during early and chronic stages of infection. Methods Illumina deep sequencing was performed for all samples while Sanger sequencing was only performed on baseline samples. Codons under immune selection pressure were assessed by computing nonsynonymous to synonymous mutation ratios using MEGA. Minority CTL epitope variants occurring at $$\ge$$ ≥ 5% were detected using low-frequency variant tool in CLC Genomics. Los Alamos HIV database was used for mapping mutations to known HIV-1 CTL epitopes. Results Fifty-two participants were enrolled in the study. Their median age was 28 years (interquartile range: 24–32 years) and majority of participants (92.3%) were female. Illumina minority variant analysis identified a significantly higher number of CTL epitopes (n = 65) compared to epitopes (n = 8) identified through Sanger sequencing. Most of the identified epitopes mapped to reverse transcriptase (RT) and integrase (IN) regardless of sequencing method. There was a significantly higher proportion of minority variant epitopes in RT (n = 39, 60.0%) compared to IN (n = 17, 26.2%) and PR (n = 9, 13.8%), p = 0.002 and < 0.0001, respectively. However, no significant difference was observed between the proportion of minority variant epitopes in IN versus PR, p = 0.06. Some epitopes were detected in either early or chronic HIV-1 infection whereas others were detected in both stages. Different distribution patterns of minority variant epitopes were observed in sample pairs; with some increasing or decreasing over time, while others remained constant. Some of the identified epitopes have not been previously reported for HIV-1 subtype C. There were also variants that could not be mapped to reported CTL epitopes in the Los Alamos HIV database. Conclusion Deep sequencing revealed many Pol CTL epitopes, including some not previously reported for HIV-1 subtype C. The findings of this study support the inclusion of RT and IN epitopes in HIV-1 vaccine candidates as these proteins harbour many CTL epitopes.

show abstract

Section: Discussionmentioning

confidence: 99%

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Nkone

Loubser

Quinn

et al. 2022

Virol J

View full text Add to dashboard Cite

show abstract

“…Overall, these observations confirm that BG505 TTT folds with a conformation closely resembling those of other nativelike Env trimers. BG505 TTT elicits qualitatively improved antibody responses in mice and rabbits Simian (chimpanzee) adenovirus-derived ChAdOx1 74 and modified vaccinia Ankara (MVA) 75 are well-established vector systems for the delivery of immunogens [76][77][78][79][80][81][82][83] . ChAdOx1 was used by AstraZeneca to deliver one of the e StrepTactinXT ELISA assay with StrepTactinXT-purified SOSIP.v8, SC and TTT protein preparations against a panel of bNAbs (2G12, VRC01, PGT121, PGT145, VRC26.25, PGT151) and non-NAbs (F105).…”

Section: Resultsmentioning

confidence: 99%

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

del Moral-Sánchez,

Wee,

Xian

et al. 2024

npj Vaccines

Self Cite

View full text Add to dashboard Cite

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies.

show abstract

“…Simian (chimpanzee) adenovirus-derived ChAdOx1 75 and modified vaccinia Ankara (MVA) 76 are well-established vector systems for the delivery of immunogens [77][78][79][80][81][82][83][84] . ChAdOx1 was used by AstraZeneca to deliver one of the first effective SARS-CoV-2 vaccines 50 .…”

Section: Bg505 Ttt Elicits Qualitatively Improved Antibody Responses ...mentioning

confidence: 99%

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

del Moral-Sánchez,

Wee,

Xian

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies.

show abstract

Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

Cited by 7 publications

References 101 publications

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

Contact Info

Product

Resources

About