Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus

Awady, Mostafa K El; Tabll, Ashraf A.; Yousif, Hassan; El, Yasmine S; Reda, Mohamed; Khalil, Samy; El-Zayadi, Abdel-Rahman; Shaker, Maysa H.; Din, Noha G Bader El

doi:10.1016/j.vaccine.2009.11.059

Cited by 12 publications

(8 citation statements)

References 28 publications

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“…A promising self-adjuvanting approach, which induces a broad response, is using multiple antigenic peptide (MAP). This approach was implemented in HCV patients by El-Awady et al and was capable of inducing both antibody and T cell responses in two thirds of the patients (98, 115). …”

Section: Prospects For Peptide Vaccinationmentioning

confidence: 99%

T Cell Responses to Viral Infections â€“ Opportunities for Peptide Vaccination

et al. 2014

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An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. Proper activation of these T cells depends on professional antigen-presenting cells, such as dendritic cells (DCs). In this review, we will discuss the potential of peptide-based vaccines for prevention and treatment of viral diseases. We will describe features of an effective response against both acute and chronic infections, such as an appropriate magnitude, breadth, and quality and discuss requirements for inducing such an effective antiviral immune response. We will address modifications that affect presentation of vaccine components by DCs, including choice of antigen, adjuvants, and formulation. Furthermore, we will describe differences in design between preventive and therapeutic peptide-based vaccines. The ultimate goal in the design of preventive vaccines is to develop a universal vaccine that cross-protects against multiple strains of the virus. For therapeutic vaccines, cross-protection is of less importance, but enhancing existing T cell responses is essential. Although peptide vaccination is successful in inducing responses in human papillomavirus (HPV) infected patients, there are still several challenges such as choosing the right target epitopes, choosing safe adjuvants that improve immunogenicity of these epitopes, and steering the immune response in the desired direction. We will conclude with an overview of the current status of peptide vaccination, hurdles to overcome, and prospects for the future.

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Section: Prospects For Peptide Vaccinationmentioning

confidence: 99%

T Cell Responses to Viral Infections â€“ Opportunities for Peptide Vaccination

et al. 2014

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“…This approach seems to be interesting, because the immune response generated against designed peptide could be directed to immunodominant protective epitopes in native proteins. Synthetic peptide based vaccines have been studied as a strategy against malaria [ 62 ], hepatitis C [ 63 , 64 ], foot-and-mouth disease [ 65 ], human papilloma virus [ 66 ] and Toxoplasma gondii [ 67 ]. Vaccination experiments using synthetic peptide from R. microplus Bm86 and Plasmodium falciparum also induced antibodies that recognized proteins from which the amino acid sequence had originated [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Rhipicephalus microplus and Ixodes ovatus cystatins in tick blood digestion and evasion of host immune response

et al. 2015

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BackgroundCystatins are a group of cysteine protease inhibitors responsible for physiological proteolysis regulation and present in a wide range of organisms. Studies about this class of inhibitors in parasites have contributed to clarify their roles in important physiological processes, like blood digestion and modulation of host immune response during blood feeding. Thus, cystatins are a subject of research on the development of new parasite control methods. Additionally, the characterization of proteins shared by different parasite species represents a valuable strategy to find potential targets in multi-species control methods. However, cystatin functions in ticks remain undetermined, especially in Rhipicephalus microplus and Ixodes ovatus, two species that affect livestock and human health, respectively.MethodsHere we report the inhibitory profile of two R. microplus (BrBmcys2b and BrBmcys2c) and one I. ovatus (JpIocys2a) cystatins to commercial cathepsins B, C, and L. The presence of native cystatins in R. microplus tissues was analyzed using sera against recombinant BrBmcys2b and BrBmcys2c. Also, a peptide from JpIocys2a was synthesized for rabbit immunization, and this serum was used to analyze the cross antigenicity between R. microplus and I. ovatus cystatins.ResultsEnzymatic inhibition profile of tick cystatins shows a distinct modulation for cathepsins related to tick blood digestion and evasion of host immune response. Furthermore, BrBmcys2b was detected in saliva and different tissues along tick stages, while BrBmcys2c was detected mainly in gut from partially engorged R. microplus females, demonstrating a distinct pattern of cystatin expression, secretion and traffic between tick tissues. Moreover, phylogenetic analysis suggests that JpIocys2a belongs to the group of tick gut secreted cystatins. Finally, cross-antigenicity assays revealed that antibodies against the JpIocys2a peptide recognize native and recombinant R. microplus cystatins.ConclusionThe presence of these proteins in different tissues and their ability to differentially inhibit cathepsins suggest distinct roles for JpIocys2a, BrBmcys2b, and BrBmcys2c in blood digestion, egg and larvae development, and modulation of host immune response in tick physiology. The cross-antigenicity between native and recombinant cystatins supports further experiments using JpIocys2a, BrBmcys2b, and BrBmcys2c as vaccine antigens.

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“…The expression of E2 related peptide in western blots at 58 kDa upon treatment with caprine IgG only in HCV positive sera confirms earlier data [24] that it represents a deglcosylated E2 protein and suggests the presence of immunodominant conserved epitopes within the E2 gp which encompass motifs of several linear epitopes. We have recently shown that these linear epitopes stimulated humoral and cellular responses in caprines [16] and in mice [25]. The observed immunoreactivity of these peptides with human IgG in HCV positive patients suggest that those E2 epitopes are immunogenic in humans, a hypothesis awaiting confirmation in future testing of healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

Tabll

Din

et al. 2011

Virol J

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Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

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Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus

Cited by 12 publications

References 28 publications

T Cell Responses to Viral Infections â€“ Opportunities for Peptide Vaccination

T Cell Responses to Viral Infections â€“ Opportunities for Peptide Vaccination

Rhipicephalus microplus and Ixodes ovatus cystatins in tick blood digestion and evasion of host immune response

Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

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