International Journal of Antimicrobial Agents 19 (2002) 169 – 172 Review DNA vaccines against cytomegalovirus: current progress N.J. Temperton * Academic Centre for Trael Medicine and Vaccines and Department of Virology, Royal Free and Uniersity College Medical School, Rowland Hill Street, London NW 32PF, UK Abstract The development of a vaccine for the prevention of primary cytomegalovirus (CMV) infection is a major public health priority. Live attenuated virus, recombinant viral vector, recombinant protein and peptide vaccines have been studied as potential vaccine candidates. In recent years, DNA vaccination strategies have been developed for many pathogens, including CMV. This review aims to bring together many aspects of this relatively new vaccine technology as applied to current research into the development of vaccines against CMV. © 2002 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. Keywords: DNA vaccines; Cytomegalovirus; Antibody; CTL; Protection www.ischemo.org 1. Introduction The -herpesvirus, cytomegalovirus (CMV) infects the majority of individuals during their lifetime yet results in disease only in those whose immune system is immature or impaired by immunosuppressive drugs or human immunodeficiency virus. This virus infects 0.3 – 2.4% of neonates born in different countries making it the most important cause of intrauterine infection [1]. There is an estimated 1% chance of developing primary CMV infection whilst pregnant in women who enter pregnancy seronegative for CMV [2,3]. The development of a CMV vaccine for the preven- tion of primary CMV infection is thus a major public health priority. A current report from the Institute of Medicine strongly supports the development of a CMV vaccine based on the economic impact of the disease caused by this virus [4]. A study published recently by our group using a mathematical modelling approach calculated that the critical vaccination proportion re- quired for eradication of CMV in the developed world lies between 59 and 62% demonstrating that even if a putative vaccine were only 80 – 90% effective in prevent- ing primary infection, CMV could be eradicated from the population by the immunisation of 66–75% of the population, a target easily achievable given a 90% current routine paediatric immunisation rate [5]. Of the 200 genes encoded by the CMV genome [6], only a small proportion are thought to comprise the targets of immune responses necessary for protection against CMV [7]. The neutralizing antibody response against HCMV is predominantly directed against a single protein, glycoprotein B (gpUL55) [8,9] while the tegument protein pp65 (ppUL83) is a major target of the cellular immune response [10 – 12]. These antigens have formed the basis of the majority of vaccine candi- dates thus far, which encompass their use within recom- binant viral vectors [13,14], recombinant protein vaccines [15] and peptide vaccines [16]. Other candidate vaccine antigens have been proposed or studied for inclusion into a CMV vaccine. HCMV gH is a major target for complement-independent neutralizing anti- body response in animals and humans and is thus a candidate antigen [17]. gH requires the assistance of another protein, gL for transport to the cell surface [18] which may thus need to be included in the vaccine preparation. It has recently been shown that 62% of sera from HCMV-seropositive donors reacted with the HCMV gM–gN complex, which thus may represent a major antigenic target and vaccine candidate [19,20]. With regards the generation of cellular responses, the non-structural IE1-exon4 protein has been shown to be an important CTL target [21]. Over the last few years, DNA vaccines have been shown to be effective inducers of cellular and humoral responses against viral antigens [22,23]. This review aims to bring together many aspects of this new vaccine * Tel.: +44-20-7472-6400; fax: +44-20-7830-2268. E-mail address: rfucdnavaccine@hotmail.com (N.J. Temperton). 0924-8579/02/$ - $20 © 2002 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. PII:S0924-8579(01)00492-7