4.2.2. Purified inactivated virus (PIV)

• Induces a balance between reactogenicity and immunogenicity

• Stimulates neutralizing antibodies and Th1 cell-mediated immunity

• Does not contribute to immunopathogenesis (vaccine-induced enhancement)

• Dengue virus serotypes do not induce long-lasting heterotypic immunity

• Subsequent infection (especially, after a long-time interval) may lead to severe dengue

• Vaccine candidates should be evaluated in geographic areas with different transmission

To date, there are several DENV vaccines under development, with some in phase 3 safety and efficacy testing. These include inactivated, live attenuated, recombinant subunit, viral vectored, and DNA vaccines. Dengue vaccine development has aimed to elicit a neutralizing antibody response, as T cells are assumed to contribute a minor or secondary role in dengue

The fundamental aim of vaccination is to promote protective immunity while avoiding disease from the vaccine itself. The first generation of viral vaccines was based on empirical attenuation by repeated passage in cultured cells. Several LAVs are eligible vaccines as they meet the following criteria; they elicit a strong and protective immune response with a low risk of disease from the vaccine itself. In the present regulatory environment, the use of LAVs has

• No suitable or ideal animal model exists for immunization studies

vaccine-mediated protection. Next, we will describe each of these vaccines.

• No well-established viral virulence markers are available

• Correlates of protection are not well defined

• Induces long-lasting immunity, safety, and protection • Generates neutralizing immunity to all four serotypes

• Suitable for use in target age groups

152 Dengue Fever - a Resilient Threat in the Face of Innovation

• Easy storage and transportation

• Existing possibility of triggering ADE

• Affordable and cost effective

• Vaccine must be tetravalent

4.1.2. Challenges

patterns [3].

4.2. Vaccine types

4.2.1. Live-attenuated virus (LAV)

• Genetically stable

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