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Vaccines for the 21st Century: A Tool for Decisionmaking
Researchers do not at present have a marker of host immune response that is predictive of vaccine efficacy. Both neutralizing antibodies and cell-mediated immune responses have been investigated and eliminated.
Gamma-134.5-deletion vaccines will eventually be tested in immunocompromised models.
Subunit vaccines currently require three doses to provide persistent antibody levels, although the duration and intensity of immune response may increase with a new adjuvant. R-70–20 acted more like a dead vaccine, requiring two doses. There are hopes that replication-competent viruses like the 134.5-deletion mutants will provide enhanced immunogenic effects with one shot rather than two.
There has been little work on cellular responses to these vaccines or indeed to primary and recurrent herpes at all. Some researchers are doing CTLs on mice, and others are looking at T-cell responses in humans who are seropositive but have no clinical recurrences. T-cell responses following primary infection are robust, but no one has done comprehensive CTLs or tried to dissect out specific T-cell response in all of these human populations.
The target population for HSV-2 immunization is adolescents as they are about to begin sexual activity, perhaps 10 or 12 years old, and the vaccine should provide at least 10 years of resistance to the wild-type virus. It will probably be impractical to test for serologic status for HSV-1 or HSV-2 prior to immunization.
Epstein-Barr virus (EBV) is another extremely common virus, but it is linked to a growing list of pathologies. Unlike HSV, there have been few vaccine trials, but a great deal is known about the disease processes. This knowledge could be used to generate partial or complete immunity to block these diseases.
Incidence and Burden. Worldwide, about 95 percent of the adult population is infected with EBV. If the primary infection comes in late adolescence, about 50 percent of seronegatives will develop the clinical manifestation called infectious mononucleosis (IM). IM is a significant disease, with at least 125,000 new cases recorded each year in the United States. About 70 percent of patient will resolve their symptoms in 2 to 4 weeks and is the major cause of lost time for new Army recruits. However, 30 percent develop more extensive impairment that may not resolve for 3 to 4 months. About 1 percent of cases develop complications, including neurological, bone marrow, liver involvement, and