Epidemiological studies demonstrate that HTLV-I is endemic in Japan, the Caribbean, Central America, and certain parts of the African continent, The number of people worldwide infected with HTLV-I alone has been estimated at between 10 and 20 million, with 1-5% ultimately developing disease. A vaccine against HTLV-I is desperately needed to control the spread of this serious illness.
In order to design a vaccine for HTLV-I, it is first necessary to document and understand the immune responses elicited against this retrovirus. Like other retroviruses, the envelope glycoproteins of HTLV-I can act as major antigens that induce serum antibodies in infected individuals. It has been demonstrated that both monkeys and rabbits can be productively infected with this retrovirus, thus providing animal models for HTLV-I infection and vaccine development.2021
Research from several groups suggests that humoral immune responses alone may be sufficient to protect against infection, and that a vaccine based on the HTLV-I envelope glycoproteins may be feasible. It has been shown that antibodies against the HTLV-I envelope glycoprotein have the ability to protect monkeys from challenge with cell-associated HTLV-I.22 Antienvelope antibodies in patient sera have been shown to cross-neutralize HTLV-I strains originating from disparate geographic regions around the world. Therefore, a vaccine developed against one strain may be effective in neutralizing other strains.23 Additionally, maternal antibodies delivered through breast-feeding are able to provide newborns with immunity and protection from congenital transmission.24
Generally, traditional vaccination has relied on either inactivated/ subunit preparations or live attenuated infectious material for the generation of a protective immune response. Inactivated or subunit vaccines provide protection through the induction of protective T helper (Th) cell and humoral immunity, but do not induce significant cytotoxic T lymphocyte (CTL) immunity. In contrast, live attenuated vaccines induce protective CTLs as well as Th cells and humoral immunity through a nonpathogenic infection of the host. This induction of MHC class I-restricted CTL immunity is thought to be crucial for protection from many viral infections. The importance of cellular immune responses in protection from HTLV-I infection is not clearly identified. It is likely that cellular responses do play a positive role in protection along with humoral responses.
A novel immunization strategy, DNA or nucleic acid vaccination, elicits both humoral and cellular immune responses in vivo. Since DNA vaccines are nonreplicating and the vaccine components are produced within the host cells, they can be constructed to function with all the safety features as well as the specificity of a subunit vaccine. However, DNA vaccine cassettes could produce immunological responses that are more similar to live vaccine preparations. By directly introducing DNA into the host cell, the host cell is essentially directed to produce the antigenic protein inside the cell thus mimicking viral replication in host cells.25-28 Accordingly, this process has been demonstrated to generate both antibody and cell-mediated, particularly killer T cell-mediated, protective immunity. Unlike the attenuated vaccine, there is a little risk for pathogenesis by reversion to a disease-causing form with the injected DNA.2930
We have investigated the ability of plasmid DNA inoculation to elicit protective immune responses against retroviruses in mice, rats, rabbits, monkeys, and chimpanzees.25-28 Our work on the HTLV-I-envelope DNA plasmid vaccines in the rabbit and rat models for this retrovirus demonstrates the induction of humoral and cellular immune responses in the animal systems. Our data and the work of others suggest the potential utility of the DNA plasmid vaccine as well as other HTLV vaccine candidates.
Another possible vaccine strategy is the generation of protein subunits that will block the binding and fusion of HTLV to target cells. In order to block binding and fusion successfully, we must first identify the HTLV receptor. Knowledge of the cellular receptor could aid attempts to understand HTLV-I infection and help focus efforts to develop therapeutic and prophylactic agents for HTLV and related viruses.
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