Vaccine 21 (2003) 419–430 Review Memory T cells and vaccines Mark T. Esser a , Rocio D. Marchese a , Lisa S. Kierstead a , Lynda G. Tussey b , Fubao Wang a , Narendra Chirmule a , Michael W. Washabaugh a,∗ a Clinical Assay Research and Development, MRL-Wayne, 466 Devon Park Drive, Wayne, PA 19087-8630, USA b Virus and Cell Biology, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486-0004, USA Received 20 November 2001; received in revised form 2 April 2002; accepted 1 August 2002 Abstract T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to na¨ ıve T cells. These na¨ ıve T cells are stimulated to proliferate and differentiate into effector and memory T cells. Activated, effector and memory T cells provide B cell help in the lymph nodes and traffic to sites of infection where they secrete anti-microbial cytokines and kill infected cells. At least two types of memory cells have been defined in humans based on their functional and migratory properties. T central-memory (T CM ) cells are found predominantly in lymphoid organs and can not be immediately activated, whereas T effector-memory (T EM ) cells are found predominantly in peripheral tissue and sites of inflammation and exhibit rapid effector function. Most currently licensed vaccines induce antibody responses capable of mediating long-term protection against lytic viruses such as influenza and small pox. In contrast, vaccines against chronic pathogens that require cell-mediated immune responses to control, such as malaria, Mycobacterium tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis C virus (HCV), are currently not available or are ineffective. Understanding the mechanisms by which long-lived cellular immune responses are generated following vaccination should facilitate the development of safe and effective vaccines against these emerging diseases. Here, we review the current literature with respect to memory T cells and their implications to vaccine development. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Vaccine; Memory; T lymphocyte; Virus; Adjuvant; Cytokine 1. Introduction Evidence for immunological memory has been recognized for more than 2000 years. Thucydides, in his description of the Peloponnesian war in 430 b.c., wrote that the deadly plague of Athens never attacked the same man twice [1]. The observation that immunological memory to a virus can last a lifetime was first recorded in 1846 by Panum [2]. Panum, a Danish physician, observed that elderly people on the Faeroes islands infected with the measles virus in 1781 were immune to a measles epidemic that struck the island more than 65 years later in 1846 [2]. Although Edward Jen- ner is credited with being the father of modern vaccination, some of the first efforts to vaccinate individuals occurred as early as the 16th century a.d. in China. The Chinese prac- ticed variolation to induce immunity by infecting healthy ∗ Corresponding author. Present address: Clinical Assay Research and Development, Merck and Co. Inc., WP17-101, PO Box 4, West Point, PA 19486, USA. Tel.: +1-215-652-3887; fax: +1-215-993-1146. E-mail address: michael washabaugh@merck.com (M.W. Washabaugh). people with a mild case of smallpox by sniffing powdered smallpox scabs or wearing the undergarments of an infected individual [3]. Variolation became popular throughout Eu- rope and the British colonies in the 18th century, but be- cause of its inherent risks (2–3% mortality rates), was not ideal [4]. By the late 1700s, Edward Jenner provided the first scientific rational for vaccination by demonstrating that in- dividuals immunized with the cowpox virus were protected from disease caused by the small pox virus [5]. The success of this first vaccine is evidenced by the fact that small pox was eliminated from the human population in 1981 [6]. The success of a variety of vaccines against bacterial and viral diseases have dramatically reduced morbidity and mor- tality worldwide. Modern vaccines have controlled at least ten major diseases that used to kill millions of people world- wide on a yearly basis. These diseases include smallpox, diphtheria, tetanus, yellow fever, pertussis, Haemophilus in- fluenzae type b, poliomyelitis, measles, mumps and rubella [7]. Poliomyelitis has not been reported in the Americas and the western Pacific since 1995 and the World Health Organi- zation (WHO) has targeted Polio for worldwide eradication 0264-410X/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(02)00407-3