An alternative approach to the development of a CMV vaccine has been to utilise DNA vaccination to induce host responses to CMV gB and phosphoprotein 65 (pp65 is another viral target). Recent studies have shown that injection of combinations of plasmids, formulated with an adjuvant, can induce vaccine-specific immune responses, and can
prime for effective memory responses. The hallmark of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) is their ability to establish and maintain latent infection in sensory ganglion neurons. Periodic reactivation of the latent infection results in recurrent infections. Both HSV-1 PFT�� and HSV-2 can cause myriad diseases but the greatest public health problem is genital herpes. Genital HSV-2 infection increases the risk of HIV acquisition and transmission, and control of genital herpes has been predicted to
significantly impact the HIV epidemic. Given the complex natural history of HSV infections, vaccines could have a variety of possible risks and benefits (Table 6.10). An effective HSV SP600125 in vitro vaccine has been sought for more than 80 years. Recently, an HSV-2 glycoprotein D (gD2) candidate vaccine containing the AS04 adjuvant (see Chapter 4 – Vaccine adjuvants), was tested in three large, double-blind, Phase III controlled trials. The first two studies recruited volunteers with a partner with genital herpes disease and found the candidate vaccine was 73% effective against genital herpes disease in women seronegative for both HSV-1 and HSV-2 ( Stanberry et al., 2002). Trends towards protection against infection were also observed, but were not statistically significant. The candidate vaccine was not effective in HSV-1 seropositive women; or in men, regardless of their HSV seropositivity status. These were the first studies to report a significant difference in vaccine efficacy between men and women. This Tolmetin finding could have important implications for other vaccines targeting sexually transmitted diseases. The basis for this difference could relate to differences in how men and women respond to novel adjuvants or may reflect differences in the acquisition and natural history of
genital herpes in men and women. A third Phase III efficacy trial of the gD2 candidate vaccine in HSV-1 and HSV-2 negative women who thought themselves possibly at risk of acquiring genital herpes (a different risk population than in the original two trials) has been completed and is being analysed. An initial assessment of the results of the third trial showed that the vaccine had an acceptable safety profile but the primary trial endpoint, prevention of genital herpes disease, was not met ( NIAID, 2010). Although the development of the vaccine has been stopped, further analyses and comparison of the trials may guide researchers as they continue seeking vaccines to control HSV infections. As discussed in Chapter 2 – Vaccine immunology, some pathogens have complex life cycles.