Prime boost regimens for enhancing immunity: Magnitude, quality of mucosal and systemic gene vaccines

The use of therapeutic or prophylactic vaccines against numerous infectious agents has been well documented. The hallmark of most vaccine strategies is to mimic infection and induce immunological memory that has the potential to confer protection. The use of live attenuated viruses, killed viruses and recombinant viral proteins for vaccination are classical vaccine approaches that have successfully induced protective antibody and cell mediated immune responses (CMI) against viruses such as small pox, influenza, polio, mumps, measles, and rubella. Despite the successes of classical vaccine approaches, these have been ineffective against chronic and highly pathogenic diseases such as human immunodeficiency virus-1 (HIV-1), tuberculosis (TB) or malaria. Hence, this paved the way for the emergence of range of novel vaccine approaches. In particular, the use of recombinant vector technologies such as the use of recombinant DNA (rDNA) or recombinant live virus vectors encoding single or multiple epitopes used in prime-boost vaccination strategies have exhibited immense potential for generating excellent immunity against intracellular pathogens such as M. tuberculosis, HIV-1, simian immunodeficiency virus (SIV), Plasmodium, Leishmania, S. mansoni, hepatitis C virus, herpes simplex virus and hepatitis B virus. In this chapter, we discuss the use of gene based heterologous prime-boost immunisation strategies for improved vaccination against intracellular pathogens, particularly with respect to HIV-1, given that prime-boost vaccine strategies have been extensively tested and studied against this virus in animal models as well as in humans.