The rational design of vaccines

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Abstract

Vaccines have potential in the control of diseases ranging from cancers and allergy to significant pathogens such as HIV and TB. However, is our current knowledge of immunological interactions in disease able to facilitate the rational design of effective vaccines?

Abstract

This review provides an insight into the various opportunities for vaccine intervention, analysis of strategies for vaccine development, vaccine ability to modulate immune responses and resultant rational vaccine design. In addition, wider aspects are considered, such as biotechnological advances, advances in immunological understanding and host–pathogen interactions. The key question addressed here is, with all our research and understanding, have we reached a new echelon in vaccine development, that of rational design?

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Most cited references 48

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Disseminated tuberculosis in interferon gamma gene-disrupted mice

DG Russell, DJ Russel, TA Stewart … (1993)

The expression of protective immunity to Mycobacterium tuberculosis in mice is mediated by T lymphocytes that secrete cytokines. These molecules then mediate a variety of roles, including the activation of parasitized host macrophages, and the recruitment of other mononuclear phagocytes to the site of the infection in order to initiate granuloma formation. Among these cytokines, interferon gamma (IFN-gamma) is believed to play a key role is these events. In confirmation of this hypothesis, we show in this study that mice in which the IFN-gamma gene has been disrupted were unable to contain or control a normally sublethal dose of M. tuberculosis, delivered either intravenously or aerogenically. In such mice, a progressive and widespread tissue destruction and necrosis, associated with very high numbers of acid- fast bacilli, was observed. In contrast, despite the lack of protective immunity, some DTH-like reactivity could still be elicited. These data, therefore, indicate that although IFN-gamma may not be needed for DTH expression, it plays a pivotal and essential role in protective cellular immunity to tuberculosis infection.

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Improved green fluorescent protein by molecular evolution using DNA shuffling.

A Crameri, E A Whitehorn, E. Tate … (1996)

Green fluorescent protein (GFP) has rapidly become a widely used reporter of gene regulation. However, for many organisms, particularly eukaryotes, a stronger whole cell fluorescence signal is desirable. We constructed a synthetic GFP gene with improved codon usage and performed recursive cycles of DNA shuffling followed by screening for the brightest E. coli colonies. A visual screen using UV light, rather than FACS selection, was used to avoid red-shifting the excitation maximum. After 3 cycles of DNA shuffling, a mutant was obtained with a whole cell fluorescence signal that was 45-fold greater than a standard, the commercially available Clontech plasmid pGFP. The expression level in E. coli was unaltered at about 75% of total protein. The emission and excitation maxima were also unchanged. Whereas in E. coli most of the wildtype GFP ends up in inclusion bodies, unable to activate its chromophore, most of the mutant protein is soluble and active. Three amino acid mutations appear to guide the mutant protein into the native folding pathway rather than toward aggregation. Expressed in Chinese Hamster Ovary (CHO) cells, this shuffled GFP mutant showed a 42-fold improvement over wildtype GFP sequence, and is easily detected with UV light in a wide range of assays. The results demonstrate how molecular evolution can solve a complex practical problem without needing to first identify which process is limiting. DNA shuffling can be combined with screening of a moderate number of mutants. We envision that the combination of DNA shuffling and high throughput screening will be a powerful tool for the optimization of many commercially important enzymes for which selections do not exist.

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Immunotherapy and chemotherapy--a practical partnership.

Georgeanna Robinson, Iain Lake (2005)

This article discusses how recent data have altered the way we understand how dying tumour cells, particularly those killed by chemotherapy, engage with antitumour immune responses. These data have significant implications for the development of new protocols combining chemotherapy with immunotherapy, indicating an exciting potential for therapeutic synergy with general applicability to many cancer types.

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Author and article information

Contributors

Yvonne Perrie

Journal

Journal ID (nlm-ta): Drug Discov Today

Journal ID (iso-abbrev): Drug Discov. Today

Title: Drug Discovery Today

Publisher: Elsevier Ltd.

ISSN (Print): 1359-6446

ISSN (Electronic): 1878-5832

Publication date PMC-release: 27 October 2005

Publication date (Print): 15 November 2005

Publication date (Electronic): 27 October 2005

Volume: 10

Issue: 22

Pages: 1527-1534

Affiliations

Medicines Research Unit, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK

Article

Publisher ID: S1359-6446(05)03600-7

DOI: 10.1016/S1359-6446(05)03600-7

PMC ID: 7108399

PubMed ID: 16257375

SO-VID: 762c2557-a384-4cef-9bf8-8dcf32466463

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Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

The rational design of vaccines

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Vaccines

Most cited references 48

Disseminated tuberculosis in interferon gamma gene-disrupted mice

Improved green fluorescent protein by molecular evolution using DNA shuffling.

Immunotherapy and chemotherapy--a practical partnership.

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