4.1.1. Characteristics


also been limited by safety concerns, including reversion to wild-type virulence. Because LAVs are shed from vaccines, they sometimes present a risk to unvaccinated individuals with impaired immunity. Although LAV vaccines have been developed for many RNA viruses, the

Current Status of Vaccines against Dengue Virus http://dx.doi.org/10.5772/intechopen.80820 153

It is widely believed that inactivated dengue virus vaccines are impractical given the difficulty in obtaining sufficiently high titers of the virus in a suitable cell substrate. However, this was challenged when dengue type-2 (dengue-2) virus was adapted to replicate to high titers in certified Vero and fetal rhesus lung (FRhL-2) cell cultures and used to make prototype purified, inactivated virus (PIV) vaccines. In addition, in formulation with an aluminum hydroxide adjuvant, these vaccines elicit virus-neutralizing antibodies in mice and rhesus macaques and

Recombinant subunit-based vaccines may prove to be significantly advantageous compared to other approaches currently being implemented for development of a dengue vaccine. First of all, the lack of a replicating virus helps to ensure the safety of the product by avoiding the possibility for inadequate attenuation or reversion in the context of live virus approaches, or inadequate inactivation in the context of killed virus vaccines. Furthermore, under a tetravalent formulation, the ability to induce a balanced immune response may be more easily manipulated through dose adjustments using recombinant subunits compared to four replicating viruses. Finally, in terms of yield and cost effectiveness, and since the dengue vaccine mainly targets developing areas, a high yielding, highly immunogenic, recombinant subunit could prove to be an attractive alternative to vaccines based on virus replication, (live attenu-

Recombinant subunit vaccines stand as one of the safest alternatives, as a means to bypass the issue of viral interference, offering the possibility to administer a tetravalent formulation on an accelerated schedule. An advantage of an accelerated schedule is that full protective immunity could be induced more quickly, thus avoiding the potential of exacerbated disease due to partial immunity during an extended immunization course. Among other advantages of an accelerated schedule are better general compliance, more suitability for travelers and military personnel, easier integration into existing immunization schedules, and the potential for use in an outbreak setting. A balanced tetravalent immune response may also be more readily accomplished through simple dose adjustments for each of the four recombinant proteins, in comparison to live virus vaccines where the interactions between viruses can be complex and unpredictable [24].

VLP vaccines are virus-like particles that do not contain replicative genetic material, but permit presentation of antigen in a repetitive, ordered array similar to the virion structure, which is thought to increase immunogenicity [25]. Thus, the safety concerns of virus vaccines regarding reversion mutants and immunocompromised individuals are obviated. The recombinant of

mutability of these pathogens presents unique challenges for vaccine design [21].

provide at least partial protection against virus challenge [22].

ated or killed) where yields may be lower than required [23].

4.2.2. Purified inactivated virus (PIV)

4.2.3. Recombinant subunits

4.2.4. Virus-like particles (VLPs)

