Vaccine 19 (2001) 2692–2700 The role of mass spectrometry in vaccine development Gregory A. Poland a, *, Inna G. Ovsyannikova a , Kenneth L. Johnson b , Stephen Naylor b a Mayo Vaccine Research Group, Department of Internal Medicine, Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street, SW, Rochester, MN 55905, USA b Biomedical Mass Spectrometry and Functional Proteomics Facility and Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, C-009B Guggenheim Building, 200 First Street, SW, Rochester, MN 55905, USA Abstract For the most part, vaccine development to date has been empiric. While sometimes successful, such a strategy is ‘hit or miss’, and fails to advance the basic science of vaccine development. Preferable would be tools that allow for a more directed development of vaccines at either the population or sub-population level. Characteristics of useful tools in vaccine development should include the ability to identify and characterize the spectrum of antigenic peptides presented by MHC molecules to which the immune system responds by the development of protective immune responses. In addition, because the explosion in human genomics allows the ability to understand MHC haplotypes at the population level, as well as an enhanced understanding of MHC binding motifs, new tools might further allow for an understanding of which vaccine antigens are capable of being bound and presented to the immune system by MHC molecules. New mass spectrometry technology fulfils these criteria, and may well lead to a revolution in the design of new vaccines. This paper will review the basics of mass spectrometry techniques as applied to the identification and characterization of vaccine peptide antigens, and discusses how these tools can be applied to vaccine development. © 2001 Elsevier Science Ltd. All rights reserved. Keywords: HLA; Vaccine development; Mass spectrometry www.elsevier.com/locate/vaccine 1. Introduction The future for vaccine development may move away from traditional vaccines containing live, attenuated (measles, mumps, rubella, varicella) or whole, inacti- vated (polio) microbial organisms or antigenic subunits of these pathogens (pertussis, pneumococcus). The trend has been towards subunit or recombinant vac- cines (hepatitis B) containing only the antigenic compo- nents necessary to induce specifically desired immune responses [1,2]. For many diseases we still lack an effective vaccine and traditional vaccination strategies may not be appropriate, either due to safety issues or lack of immune potency [3]. Therefore, it is imperative that new approaches to vaccine development continue to be explored. Recent efforts to produce new and improved vaccines have concentrated on studying the immune responses to infectious diseases and pathogens with the aim of ultimately identifying antigenic sites on pathogens that are involved in stimulating an appropri- ate protective immune response [4,5]. For decades efforts in vaccine development have been directed primarily towards the preparation of vaccines able to elicit protective antibodies to toxins and pathogens [6]. In the past decade significant pro- gress has particularly been made in understanding the functions of T lymphocytes in the role of immunity [7,8]. The T cells of the human immune system recog- nize immunogenic peptides bound to the human leuko- cyte antigen (HLA) genes (also known as MHC genes, or major histocompatibility complex) expressed on the surface of antigen-presenting cells (APCs) [2]. The spe- cificity of this recognition is defined not only by the primary sequence of the specific peptide but also by the specific HLA molecule with which the peptide is selec- tively associated [9]. As such, HLA-associated peptides are critical in the functioning of the immune system, and HLA class I and class II molecules present a * Corresponding author. Tel.: +1-507-2844968; fax: +1-507- 2664716. E-mail address: poland.gregory@mayo.edu (G.A. Poland). 0264-410X/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(00)00505-3