Vaccines for several other viral diseases are currently in the early stages of development. At least four different types of hepatitis C vaccines are in preclinical development. However, research for these candidate vaccines is hampered by the lack of reproducible tissue culture or a convenient small animal model for testing (212). Early studies in chimpanzees with several hepatitis C vaccines are currently underway.
Three different Epstein-Barr virus vaccine types are reported to be in phase I studies, including a glycoprotein sub- unit (gp350) vaccine, a vaccinia recombinant vaccine express- ing gp350, and peptide induction of cutaneous T lymphocytes (212). It is yet unknown if the speciﬁc antigenic components of these vaccines are sufﬁcient to prevent infection.
At least 14 different vaccines are under development for dengue virus. While most are in preclinical stages, a combined quadrivalent vaccine is in phase I trials. The live-attenuated vaccines have shown encouraging promise in the prevention of infection (212).
Viral vaccine development continues to move away from classical live-attenuated vaccines towards whole inactivated virus vaccines, peptide-based vaccines, DNA-based vaccines, use of viral vectors to insert recombinant information in vac- cines, human immune globulins, monoclonal antibodies, and recombinant humanized vaccines, such as product production standardization, sustained immunological response, technical feasibility, less reactogenic, and nontransmissable or non- pathogenic to humans. However, there are challenges to the use of these new technologies, such as reliable efﬁcacy and potency, need for an adjuvant or delivery system, or estab- lishement of proof of principal.
Perhaps the greatest challenge is the expectation that a vaccine will be 100% effective and safe for every vaccinee. One death among 1 million vaccinees is considered excessive. How- ever, without the vaccine, many more may die from the dis- ease. Such is the case with the withdrawn approval of the rotavirus vaccine, when up to 600,000 children from developing countries die each year from dehydration and diarrhea. Adju- vants enhance the effect of the vaccine and may permit lower dosage levels and lower number of dosages. They may provide better mucosal immunity, more protection for the immuno- compromised, and better antibody response (326).