Synthetic peptides as the basis for future vaccines

doi:10.1016/0968-0004(86)90088-5

Trends in Biochemical Sciences

Volume 11, Issue 12, December 1986, Pages 521-524

https://doi.org/10.1016/0968-0004(86)90088-5 Get rights and content

Abstract

Synthetic peptides corresponding to epitopes of proteins are capable of eliciting a specific immune response to the intact native protein. Consequently, it is feasible to use synthetic peptide ‘vaccines’ to induce protective immunity against infections by microorganisms including bacteria, viruses and even parasites. Furthermore, immunity against hormonal peptides may lead to means of immunological contraception, thus demonstrating the wide-ranging applicability of this approach.

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Cited by (35)

Human IgG1 hinge-fragment as a core structure for immunogens
1995, Studies in Natural Products Chemistry
After the early discovery that synthetic fragments of proteins if suitably presented to the immune system, are capable of eliciting antibody responses cross-reactive with the parent proteins, the concept of synthetic vaccines has become a main target in immunology. Today there are well-established tenets that generation of the humoral response requires cooperation and communication between B and T cells and that small-sized antigens induce immunity only when appropriately presented for recognition by both the B-lymphocytes and T-helper cells. As immunological responsiveness is dependent on the HLA genotype of an individual, genetic restriction presents an additional burden for the design of fully synthetic immunogens as mimetics of surface regions of pathogens, but which nonetheless give raise to antibodies capable of neutralizing the microorganism and abolishing its infectivity. In the context of knowledge in the field our contribution is reviewed by comparing the intensity and specificity of the immune responses to a self-antigen, i.e. to the hormone gastrin, in various approaches as antigen/protein conjugates, built-in immunoadjuvanticity, liposomal preparations and finally with well defined constructs in which the hinge segment of human IgG1 with its peculiar structural and functional properties was exploited. The conservative character of the hinge as pivot in the dynamics of the immunoglobulins, and its apparently universal role as recognition site in the interplay of immunologically relevant molecules was found to induce surprisingly high immunogenicity even in the case of self-antigens indicating that such hinge-peptide/antigen constructs as interesting molecules for studying the processes of immunity at cellular level.
Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen
1995, Vaccine
The development of peptide-based vaccines that elicit antibody (Ab) and cellular immune responses has been hampered by the lack of highly immunogenic formulations. In this study, we compared the induction of Ab and cytotoxic T-lymphocyte (CTL) responses to a peptide derived from the V3 loop of HIV-1 gp120 (P18 and its cysteine-glycine derivative (CG-P18) when incorporated into liposomes with lipid A (LA) or mixed with aluminum hydroxide. P18-specific CTL were only observed with liposomes with LA. P18-specific Ab responses were found with liposomes containing CG-P18 but not P18. Increased surface expression of the former, resulted in enhancement of the Ab response without loss of CTL induction. Thus, the manner in which a peptide is localized can influence the outcome of the response induced by highly immunogenic liposome formulations.
An underexploited source of smaller alpha-peptides
1994, Bioresource Technology
Co-dominant and reciprocal T-helper cell activity of epitopic sequences and formation of junctional B-cell determinants in synthetic T:B chimeric immunogens
1993, Vaccine
The identification of defined T-helper (Th) cell determinants, particularly those recognized in the context of several MHC or HLA haplotypes, and their use to provide effective carrier help to short synthetic constructs representing a B-cell epitope have made it feasible to synthesize putatively potent immunogens. However, a number of crucial questions regarding immunogenicity of epitopic sequences need to be addressed before an optimally effective synthetic vaccine can be designed. The present study deals with the hybrid constructs incorporating a known B-cell epitope from the merozoite surface protein-1 (MSP-1) of a human malarial parasite, Plasmodium falciparum, and the promiscuous Th-cell epitope from tetanus toxin or from the circumsporozoite protein of P. falciparum. Here, we provide data which suggest that B- and T-cell determinants present in a hybrid construct could, in fact, provide reciprocal helper activity for antibody production; that antibodies to a Th-cell epitope may not necessarily block its helper function; and that functional B-cell epitopes may be formed. All this may influence, in an unpredictable manner, the quality of protective immune response sought to be generated using the chimeric immunogens, with important implications for vaccine design.
Synthetic approaches to vaccines for infectious and autoimmune diseases
1992, Vaccine
The development is outlined of some synthetic vaccines against infectious diseases, in particular cholera, shigella and influenza. In the last case, use of the synthetic adjuvant MDP in combination with a haemagglutinin peptide has led to a synthetic vaccine with built-in adjuvanticity. The production of vaccines both by chemical synthesis and genetic engineering is described. The successful use of the synthetic amino acid copolymer COP-1 as an immunomodulatory vaccine to suppress the onset of allergic encephalomyelitis in experimental animals has led to clinical trials with patients suffering from exacerbating remitting multiple sclerosis. T-cell vaccination is an alternative approach to immunization against autoimmune diseases.
Predicting antigenic sites on proteins
1991, Trends in Biotechnology
The ability to predict antigenic sites on proteins is of major importance for the production of synthetic peptide vaccines and synthetic peptide probes of antibody structure. Many predictive methods, based on various assumptions about the nature of the antigenic response have been proposed and tested. This review will discuss the principles underlying the various approaches to predicting antigenic sites and will attempt to answer the question of how well they work.

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Trends in Biochemical Sciences

ReviewSynthetic peptides as the basis for future vaccines

Abstract

Mol. Immunol.

Vaccine

Biochim. Biophys. Acta

Cell

J. Reprod. Immunol.

Science

Nature

Naturwissenschaften

Review
Synthetic peptides as the basis for future vaccines