Immunogenicity of sequences around HIV-1 protease cleavage sites: Potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites

Luo, Ma; Capiña, Rupert; Daniuk, Christina; Tuff, Jeffrey; Peters, Harold O.; Kimani, Murungaru; Wachihi, Charles; Kimani, Joshua; Ball, T. Blake; Plummer, Francis A.

doi:10.1016/j.vaccine.2013.04.057

Cited by 18 publications

(37 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, mutations that disrupt the cleavage of individual sites or alter the order in which sites are cleaved result in aberrant particles that have significantly reduced infectivity [6]. Although other publications previously reported that certain CS were more conserved than others, they only analyzed a very limited number of HIV-1 variants and site sequences [3], [27], [28]. Thus, to our knowledge, our study is the first to evaluate the conservation rate in 11 CS within Gag and GagPol precursors and to define the consensus sequences in each site using a large sequence dataset including all Group M subtypes and most CRF.…”

Section: Discussionmentioning

confidence: 99%

“…Only a limited number of studies have previously evaluated the natural variation within gag and CS [3], [5], [12], [28], [32], [33]. However, these have mainly focused on subtypes B and/or C and they have analyzed a smaller dataset or a limited number of CS in most cases.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the majority of the studies used HXB2 subtype B as reference sequence for conservation analysis [5], [32], [33], pNL-4-3subtype B [12] or the Group M most recent common ancestor sequence [3]. Only one used the consensus-of-consensuses sequence provided by GenBank as a reference for comparisons [28]. None inferred a consensus sequences for each analyzed HIV-1 variant and site.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that sequences around the CS in Gag are equally conserved as functional motives and sequences targeted by RT inhibitors and are more conserved than non-functional motives [28]. These authors suggested that the amino acid sequences overlapping the CS are immunogenic and, consequently, a vaccine targeting CS could be used for the majority of the world population [28].…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports only analyzed a limited number of HIV-1 variants and site sequences [3], [27], [28]. Thus, the goal of our descriptive analysis was to analyze, for the first time, the conservation rate at amino acid level of each individual protease CS located within Gag or Pol for all HIV-1 groups, Group M subtypes and recombinants circulating in the HIV/AIDS pandemic.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

New Findings in Cleavage Sites Variability across Groups, Subtypes and Recombinants of Human Immunodeficiency Virus Type 1

2014

View full text Add to dashboard Cite

BackgroundPolymorphisms at cleavage sites (CS) can influence Gag and Pol proteins processing by the viral protease (PR), restore viral fitness and influence the virological outcome of specific antiretroviral drugs. However, data of HIV-1 variant-associated CS variability is scarce.MethodsIn this descriptive research, we examine the effect of HIV-1 variants on CS conservation using all 9,028 gag and 3,906 pol HIV-1 sequences deposited in GenBank, focusing on the 110 residues (10 per site) involved at 11 CS: P17/P24, P24/P2, P2/P7, P7/P1, P1/P6gag, NC/TFP, TFP/P6pol, P6pol/PR, PR/RTp51, RTp51/RTp66 and RTp66/IN. CS consensus amino acid sequences across HIV-1 groups (M, O, N, P), group M 9 subtypes and 51 circulating recombinant forms (CRF) were inferred from our alignments and compared to the HIV-1 consensus-of-consensuses sequence provided by GenBank.ResultsIn all HIV-1 variants, the most conserved CS were PR/RTp51, RTp51/RTp66, P24/P2 and RTp66/IN and the least P2/P7 and P6pol/PR. Conservation was significantly lower in subtypes vs. recombinants in P2/P7 and TFP/P6pol and higher in P17/P24. We found a significantly higher conservation rate among Group M vs. non-M Groups HIV-1. The late processing sites at Gag (P7/P1) and GagPol precursors (PR/RTp51) presented a significantly higher conservation vs. the first CS (P2/P7) in the 4 HIV-1 groups. Here we show 52 highly conserved residues across HIV-1 variants in 11 CS and the amino acid consensus sequence in each HIV-1 group and HIV-1 group M variant for each 11 CS.ConclusionsThis is the first study to describe the CS conservation level across all HIV-1 variants and 11 sites in one of the largest available sequence HIV-1 dataset. These results could help other researchers for the future design of both novel antiretroviral agents acting as maturation inhibitors as well as for vaccine targeting CS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

New Findings in Cleavage Sites Variability across Groups, Subtypes and Recombinants of Human Immunodeficiency Virus Type 1

2014

View full text Add to dashboard Cite

show abstract

Immunogenicity of different nanoparticle adjuvants containing recombinant RBD coronavirus antigen in animal model

Ataei,

Ahmadi,

Fasihi‐R

et al. 2023

Biotech and App Biochem

View full text Add to dashboard Cite

Ongoing mutations of SARS‐CoV‐2 present challenges for vaccine development, promising renewed global efforts to create more effective vaccines against coronavirus disease (COVID‐19). One approach is to target highly immunogenic viral proteins, such as the spike receptor binding domain (RBD), which can stimulate the production of potent neutralizing antibodies. This study aimed to design and test a subunit vaccine candidate based on the RBD. Bioinformatics analysis identified antigenic regions of the RBD for recombinant protein design. In silico analysis identified the RBD region as a feasible target for designing a recombinant vaccine. Bioinformatics tools predicted the stability and antigenicity of epitopes, and a 3D model of the RBD‐angiotensin‐converting enzyme 2 complex was constructed using molecular docking and codon optimization. The resulting construct was cloned into the pET‐28a (+) vector and successfully expressed in Escherichia coli BL21DE3. As evidenced by sodium dodecyl‐polyacrylamide gel electrophoresis and Western blotting analyses, the affinity purification of RBD antigens produced high‐quality products. Mice were immunized with the RBD antigen alone or combined with aluminum hydroxide (AlOH), calcium phosphate (CaP), or zinc oxide (ZnO) nanoparticles (NPs) as adjuvants. Enzyme‐linked immunosorbent assay assays were used to evaluate immune responses in mice. In‐silico analysis confirmed the stability and antigenicity of the designed protein structure. RBD with CaP NPs generated the highest immunoglobulin G titer compared to AlOH and ZnO after three doses, indicating its effectiveness as a vaccine platform. In conclusion, the recombinant RBD antigen administered with CaP adjuvant NPs induces potent humoral immunity in mice, supporting further vaccine development. These results contribute to ongoing efforts to develop more effective COVID‐19 vaccines.

show abstract

Nanotechnologies for the delivery of biologicals: Historical perspective and current landscape

Durán‐Lobato

López-Estévez

Cordeiro

et al. 2021

Advanced Drug Delivery Reviews

View full text Add to dashboard Cite

Immunogenicity of sequences around HIV-1 protease cleavage sites: Potential targets and population coverage analysis for a HIV vaccine targeting protease cleavage sites

Cited by 18 publications

References 46 publications

New Findings in Cleavage Sites Variability across Groups, Subtypes and Recombinants of Human Immunodeficiency Virus Type 1

New Findings in Cleavage Sites Variability across Groups, Subtypes and Recombinants of Human Immunodeficiency Virus Type 1

Immunogenicity of different nanoparticle adjuvants containing recombinant RBD coronavirus antigen in animal model

Nanotechnologies for the delivery of biologicals: Historical perspective and current landscape

Contact Info

Product

Resources

About