Strategies for genetic manipulation of RNA viruses comparable to the insertion of DNA segments in vaccinia viruses are only now being developed. Conceivably, cDNA segments could be inserted into DNA vectors, allowing for production of the antigenic proteins or peptides required to induce immunity to all four dengue serotypes. Genetic mapping of the dengue virus genome is under way (National Institute of Allergy and Infectious Diseases, 1985).
Other strategies for developing second generation vaccines include (1) engineering dengue vaccines by substituting immunoprotective epitopes into the 17D yellow fever virus and using this virus as a possible vector; (2) experimentation with other vectors, such as bacteria or other viruses; and (3) definition of epitopes that induce the formation of protective rather than enhancing antibodies in a manner similar to that demonstrated for yellow fever (Schlesinger et al., 1985).
Among the various vaccine approaches discussed above, the committe chose to evaluate an attenuated live vector virus containing the gene for a broadly cross reacting protective antigen. Such an antigen has yet to be identified; if one does not exist, or its use proves impracticable, then a vector containing a gene for a protective antigen from each of the four dengue virus types will be the preferred approach. Predictions for vaccine development are similar for either strategy.
Bancroft, W.H., R.M.Scott, K.H.Eckels, C.H.Hoke, Jr., T.E.Simms, K.D.Jesrani, P.L.Summers, D.R.Dubois, D.Tsoulos, and P.K. Russell. 1984. Dengue virus type 2 vaccine: Reactogenicity and immunogenicity in soldiers. J. Infect. Dis. 149(6):1005–1010.
Eckels, K.H., R.M.Scott, W.H.Bancroft, J.Brown, D.R.Dubois, P.L. Summers, P.K.Russell, and S.B.Halstead. 1984. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. V. Human response to immunization with a candidate vaccine prepared in fetal rhesus lung cells. Am. J. Trop. Med. Hyg. 33(4):684–689.
Halstead, S.B. 1980a. Immunological parameters of togavirus syndromes. Pp. 107–173 in Togaviruses, Biology, Structure Replication, R.W.Schlesinger, ed. New York: Academic Press.
Halstead, S.B. 1980b. Dengue hemorrhagic fever—a public health problem and a field for research. Bull. WHO 52:1–21.
Halstead, S.B. 1981a. Arboviruses and their diseases, Pacific and Southeast Asia. Pp. 1140–1149 in Textbook of Pediatric Infectious Diseases, R.D.Feigin and J.D.Cherry, eds. Philadelphia: W.B. Saunders.
Halstead, S.B. 1981b. The pathogenesis of dengue. Molecular epidemiology in infectious disease. The Alexander D.Langmuir Lecture. Am. J. Epid. 114:632–648.