Overlapping synthetic peptides as vaccines

Jiang, Shisong; Song, Ruijiang; Попов, Сергей Витальевич; Mirshahidi, Saied; Ruprecht, Ruth M.

doi:10.1016/j.vaccine.2006.04.070

Cited by 17 publications

(17 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings confirmed that an intact TM is an important factor for in vivo viral replication. Thus, we hypothesize that the TM truncation in EIAV FDDV13 is possibly an important reason for its low level of replication [13].…”

Section: Discussionmentioning

confidence: 97%

“…This investigation and some others found that this attenuation of virulence and the enhancement of immunogenicity were closely linked to multiple mutations in multiple viral genes. Using reverse mutations of selected sites of the vaccine strain to the corresponding sequence of the virulent strain, results from our laboratory and others determined that some mutations, especially consensus mutations that consistently existed in most of the successors once raised, in LTR [9,10], gp90 [11,12], gp45 [13], and S2 (manuscript in preparation) were responsible for the virulence of EIAV.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAVFDDV13

Wang

et al. 2010

Virus Genes

View full text Add to dashboard Cite

Chinese equine infectious anemia virus (EIAV) attenuated vaccine is the first lentiviral vaccine with a successful application. In order to understand the correlation of viral genomic mutations with viral attenuation and with induced immunoprotective properties, we analyzed the proviral genome sequences of the EIAV-attenuated vaccine strain EIAV(FDDV13) (EIAV fetal donkey dermal cell-adapted vaccine) and its highly virulent parental strain EIAV(LN40). The sequences of these strains were compared with those of the major foreign EIAV strains. The results indicated a large genetic distance between the Chinese EIAV strain and the major EIAV strains in America and Japan. The Chinese strains belong to an independent phylogenetic branch. The divergence between the entire genome of the Chinese strains and that of other major EIAV strains is approximately 23%. The divergence rate in LTR is over 14%, whereas that in each open reading frame is over 20%. The gp90 exhibited a divergence of 35% in its nucleotide sequence and 40% in its amino acid sequence. The present study found that after long-term passage in vitro, EIAV(FDDV13) has accumulated many stable substitution mutations in each gene. These mutations at multiple sites in multiple genes of the vaccine strain, especially the conserved mutations, provide important references for further understanding the attenuation mechanism of Chinese EIAV-attenuated vaccine and the immunoprotection mechanism of lentiviral vaccines.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAVFDDV13

Wang

et al. 2010

Virus Genes

View full text Add to dashboard Cite

show abstract

“…In our earlier mouse studies, OSP were able to induce immune responses in different strains of inbred mice as well as in the outbred mice [25, 26]; the strategy was found to be only modestly successful in RMs. This is not a stand-alone case where a mouse-tested vaccine concept could not be translated with equal success into primates/humans.…”

Section: Discussionmentioning

confidence: 99%

“…These peptides may bind directly to MHC class II molecules of antigen presenting cells (APC) and need only partial processing for binding to MHC class I molecules. In our earlier studies, this approach generated peptide-specific cellular immune responses in all vaccinated outbred mice and also in different strains of inbred mice [25, 26]. The number of peptides made available to MHC molecules after antigen processing is limited [27, 28], but MHC molecules are potentially very promiscuous and can bind to more than million different peptides with significant affinity [29].…”

Section: Introductionmentioning

confidence: 99%

Multimodality vaccination against clade C SHIV: Partial protection against mucosal challenges with a heterologous tier 2 virus

Lakhashe

Byrareddy

Zhou

et al. 2014

Vaccine

Self Cite

View full text Add to dashboard Cite

We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. This SHIV strain exhibits many properties of transmitted HIV-1, such as tier 2 phenotype (relatively difficult to neutralize), exclusive CCR5 tropism, and gradual disease progression in infected RMs. Since no human AIDS vaccine recipient is likely to encounter an HIV-1 strain that exactly matches the immunogens, we immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low-level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses.

show abstract

“…Previous publications have shown that overlapping synthetic peptides are capable of generating immune responses (12,13). Our recombinant overlapping peptide protein (ROP) covers the complete sequence of HIV Nef.…”

mentioning

confidence: 99%

Comparing Pooled Peptides with Intact Protein for Accessing Cross-presentation Pathways for Protective CD8+ and CD4+ T Cells

Zhang

Hong

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

To better understand the mechanisms of intracellular trafficking and presentation of exogenous peptides by antigen-presenting cells (APC), we compared the handling of overlapping 24-mer peptides from HIV Nef either mixed or covalently linked in tandem in one protein. Once internalized, peptides trafficked not only to endosomes but also to cytosol, and activated CD8 ؉ and CD4؉ T cells. In contrast, whole protein was found to traffic only to the endosomal compartments, and primarily activated CD4 ؉ T cells. Finally, with adjuvant, overlapping peptides were capable of protecting against lethal viral challenge, whereas the intact protein was less protective. These data suggest that overlapping long peptides are cross-presented through more varied intracellular routes and are more efficient in priming protective immunity than the whole protein.Despite much progress in vaccine development, there are still several challenges for design of subunit vaccines. Against intracellular pathogens, it is especially important to immunize protective CD4 ϩ and CD8 ϩ T cell responses. The former recognize epitopes presented by major histocompatibility complex (MHC) 3 class II molecules that are normally loaded mainly with peptides derived from exogenous antigens. Natural processing and loading are catalyzed by HLA-or H2-DM in acidic lysosomes (1).By contrast, CD8 ϩ T cell responses typically depend on epitope loading via the class I pathway. This "endogenous" route starts from the cytosol of any cells naturally infected by the relevant virus, which may not include professional antigen presenting cells (pAPCs). Once processed by cytosolic proteases, viral peptide fragments are transported into the endoplasmic reticulum, and loaded onto MHC class I molecules, which then traffic to the surface where they can present to CD8 ϩ T cells (2, 3). For exogenous antigens, "cross-presentation" by pAPCs is essential for priming CD8 ϩ as well as CD4 ϩ T cells.Although they must be crucial for most CD8 ϩ T cell vaccination strategies, the mechanisms underlying cross-presentation are not understood. First, internalized antigens are known to enter the cytoplasm, although the mechanisms remain unknown. Once in the cytoplasm, they can follow the conventional MHC class I pathway, i.e. processing by cytosolic proteasomes or proteases, transport into the endoplasmic reticulum, loading onto MHC class I molecules, and then trafficking to the surface for recognition by T cells (2, 3). Second, antigens internalized into endocytic compartments could be degraded by the local proteases into peptides and then loaded onto MHC class I molecules in the endocytic compartments that are recycled to and from the cell surface (4). Third, endosomes may fuse with the endoplasmic reticulum, allowing direct access of such peptides for loading onto nascent MHC class I molecules there before presentation at the cell surface (5); however, this theory remains controversial (6, 7).It has been hypothesized that endocytic and cytosolic proteases process antigens differently. If ...

show abstract

Overlapping synthetic peptides as vaccines

Cited by 17 publications

References 54 publications

Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAVFDDV13

Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAVFDDV13

Multimodality vaccination against clade C SHIV: Partial protection against mucosal challenges with a heterologous tier 2 virus

Comparing Pooled Peptides with Intact Protein for Accessing Cross-presentation Pathways for Protective CD8+ and CD4+ T Cells

Contact Info

Product

Resources

About