Safety and protective efficacy of INA-inactivated Venezuelan equine encephalitis virus: Implication in vaccine development

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

“…Efforts have been made to develop next generation vaccines through a number of platforms, including live-attenuated virus chimeras and targeted mutants, viral replicons (VRPs), virus-like particles (VLPs), DNAbased approaches, and an array of different inactivation techniques for whole viruses. [32][33][34][35] The number of candidate vaccines that have been developed for individual virus species is much larger than the number that has been tested for potential use as trivalent vaccines. Table 1 highlights the progress to a trivalent vaccine against WEEV, EEEV, and VEEV, which has largely focused on inactivated viruses, VRPs, VLPs, and DNA-based vaccines.…”

1,5-Iodonaphthyl azide-inactivated V3526 protects against aerosol challenge with virulent venezuelan equine encephalitis virus

“…Inactivation of V3526 by INA, therefore, was undertaken to impart another layer of safety over an already attenuated virulence profile. INA is a hydrophobic alkylating compound which covalently binds to the lipoproteins in the viral envelope without affecting the structural integrity of the surface epitopes [6,11]. Several viruses including VEEV have been shown to be inactivated by INA, while retaining their immunogenic properties [6,[11][12][13][14][15][16][17].…”

“…Sucrose gradient purified V3526 was inactivated by INA (INA-iV3526) as previously described in detail [6]. Briefly, 500 g of viral protein was mixed with 100 M INA and incubated at room temperature for 20 min.…”

“…However, its development as a vaccine candidate was stopped due to causation of adverse reactions in the vaccines during the clinical trial [5]. We have previously shown that V3526 can be completely inactivated by hydrophobic alkylating compound, 1,5-iodonaphthyl azide (INA) [6]. In this study, we evaluated the protective efficacy of INAinactivated V3526 (INA-iV3526) against aerosol challenge with virulent Trinidad donkey strain of VEEV (VEEV-TrD).…”

Dengue virus photo-inactivated in presence of 1,5-iodonaphthylazide (INA) or AMT, a psoralen compound (4′-aminomethyl-trioxsalen) is highly immunogenic in mice

“…Iodonaphthyl azide (INA) has also been used as an agent for photochemical inactivation of viruses. 22,35,36 While psoralen derivatives target pyrimidines in 22 It is not clear why INA-inactivated dengue-2 virus bound monoclonal antibodies less well compared with live virus. Intra-nasal immunization of mice with influenza virus similarly inactivated using INA induced antibodies and protected mice from live virus challenge.…”