An increased understanding of human immunology and of host–pathogen interactions should enable the identification of the type(s) of immunity required to effectively prevent or control persistent infections (see Chapter 2 – Vaccine immunology). Some examples of persistent infections are shown in Table 6.8. Mycobacterium tuberculosis can persist in a latent state within the human host
for years without causing disease (latent TB). Protection against miliary (disseminated) TB in children is provided by the bacille Calmette–Guérin (BCG) vaccine, developed through culture Selleck MK-2206 attenuation of Mycobacterium bovis early in the 20th century, which is routinely given in many countries. The vaccine, however, provides only modest and often temporary protection against pulmonary TB, and provides lower efficacy in resource-limited regions SCH772984 closer to the equator. In addition, vaccination with live, attenuated Mycobacterium bovis is a particular concern in HIV-positive individuals, especially those with advanced immune suppression; this population would particularly benefit from TB vaccination as TB is a leading cause of death worldwide for people with HIV/acquired immunodeficiency syndrome (AIDS). However, a recent Phase III trial demonstrated that protection against TB can be provided
to individuals with HIV by using an inactivated whole-cell mycobacterial vaccine ( von Reyn et al., 2010). The current state of TB vaccine development has been summarised in reviews by Walker et al. (2010) and Lambert et al. (2009) and examples of vaccines in development are shown in Table 6.9. Cytomegalovirus, a herpes virus, establishes latent infection in cells in the bone marrow and peripheral blood. Primary infection during pregnancy is associated with congenital infection that frequently causes a well-characterised spectrum of abnormalities and disabilities, which may be PRKACG severe or fatal. Reactivation in pregnancy is common, but is unlikely to cause severe congenital infection, although some manifestations,
especially hearing loss, remain common. Reactivation of CMV is of special concern in immunocompromised individuals, where severe and fatal pulmonary, hepatic and central nervous system infections are common. Gastrointestinal disease and retinitis are common in association with HIV. A successful CMV vaccine has proved elusive for more than 30 years. Based upon the observation that antibodies to the CMV envelope glycoprotein B (gB) could neutralise the virus, and with the advent of genetically engineered viral proteins, new research began in the late 1980s on a CMV gB subunit vaccine. This included the use of a novel adjuvant, MF59™ ( Pass et al., 1999). A recent Phase II clinical trial in CMV-seronegative women ≤1 year post-partum has shown the potential of gB/MF59 in decreasing incident cases of maternal and congenital CMV infection ( Pass et al., 2009).
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