Hydrophobic Inactivation of Influenza Viruses Confers Preservation of Viral Structure with Enhanced Immunogenicity

Abstract

The use of inactivated influenza virus for the development of vaccines with broad heterosubtypic protection requires selective inactivation techniques that eliminate viral infectivity while preserving structural integrity. Here we tested if a hydrophobic inactivation approach reported for retroviruses could be applied to the influenza virus.

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

“…4). These results corroborated our previous findings with V3000 strain of VEEV [26] and also with other reports of inactivation of influenza, Ebola, HIV and SIV viruses by INA [31][32][33]. Further RNA isolated from the INA-inactivated V3526 did not show any infectivity (Supplementary Fig.…”

“…Adjuvants such as CpG and Alhydrogel have been shown to enhance the antibody titers and protection in mice immunized with gamma irradiated V3526 [41]. These results are similar to those demonstrated by others with influenza and Ebola viruses where INA-inactivated viruses induced protective antibody response to respective viruses [32,33]. We also demonstrate in vitro that INA can efficiently inactivate the live attenuated vaccine strain V3526 of VEEV.…”

“…This results in the inactivation of the membrane proteins without affecting the ectodomain of these proteins that is protruding outside the membrane bilayer [29,30]. This mechanism of action of INA was exploited to inactivate other viruses such as HIV, SIV, Ebola and influenza virus [31][32][33].…”

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

“…However, the antibodies induced were generally 3-fold lower compared with that induced by live virus. 35 In contrast, we have shown that dengue-2 virus inactivated by AMT retained the ability to bind to all tested monoclonal antibodies. Although dengue virus type 1 inactivation and immunogenicity was reported previously 33,34 a comparison with other methods of inactivation, including formaldehyde inactivation has not been previously made.…”

“…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.…”