Gamma‐irradiated influenza A virus can prime for a cross‐reactive and cross‐protective immune response against influenza A viruses

Abstract

Summary A-strain influenza virus A/JAP (H2N2) was tested for its ability to induce cytotoxic T cells (Tc) after being rendered non-infectious by either UV or gamma irradiation. Gamma-irradiated virus proved to be more efficient than U V-inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells//I vitro. Most importantly, y-inactivated, but not U V-inactivated, A/JAP immunized animals survived lethal challenge with heterologous (A/PC(H3N2), A/WSN(HIN1)) virus as effectively as mice primed with infectious virus.

Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses

“…The latter observation, together with the induction of cross-protective immunity induced in IFN-IIR Ϫ/Ϫ mice, strongly suggests that the cytolytic component of Tc cells provides protection through killing of virusinfected cells via their granule-exocytosis pathway of cytotoxicity, not by CD8 ϩ T-cell IFN-␥-mediated virus control. Consistent with the above, immunization with ␥-irradiated influenza virus can elicit cross-reactive Tc-cell responses similar to those induced by live virus (34). In contrast to virus inactivation by chemical treatment, gamma irradiation leaves the functional domains of the viral proteins intact, thus facilitating efficient uptake and uncoating of viral particles, similar to the case with live virus.…”

“…The absence of serum cross-neutralizing activity between H3N2 and H1N1 influenza viruses, the lack of cross-protective immunity in defined Tc-cell-deficient knockout mice, and the results of adoptive transfer experiments indicate that cellular rather than humoral immunity plays a pivotal role in protecting mice against heterosubtypic influenza virus challenges. In addition, we have shown previously that ␥-irradiated influenza virus preparations induce cross-reactive Tc-cell responses (2,34). Thus, we tested the effect of vaccination on the kinetics of Tc-cell responses in the lung following i.n.…”

“…We reported previously that ␥-irradiated influenza viruses can confer cross-protective immunity in mice, whereas UVinactivated viruses do not (34), and we hypothesized that such inactivated influenza virus preparations may potentially be effective as universal influenza vaccines (34,35 ) were grown in 10-day-old embryonated chicken eggs. Each egg was injected with 0.1 ml normal saline containing 1 hemagglutinin unit (HAU) of virus, incubated for 48 h at 37°C, and then held at 4°C overnight.…”

Cutting Edge: Rapid and Efficient In Vivo Cytotoxicity by Cytotoxic T Cells Is Independent of Granzymes A and B

“…mice) and used according to institutional animal experimentation approval. The influenza virus A/PR8 and Hampstead egg (HE)-ECTV were grown and assayed as described previously (15,18). (19), and cell tracker-labeled (7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) or DDAO; 10 M) CD45.…”

Controlling Influenza by Cytotoxic T-Cells: Calling for Help from Destroyers

“…Some experimental adjuvants, such as ISCOMs (an immunostimulating complex already tested in humans [6, 7]), and possibly also live attenuated vaccines, can induce substantial cellular immunity. The cellular arm of the immune system can provide HSI by inducing cytotoxic T cell (CTL) immunity directed against conserved influenza virus antigens [8, 9] and combining conserved immunogenic protein sequences from different influenza virus strains might result in a vaccine that protects against most current and future circulating influenza strains [10]. Another strategy for the induction of HSI shown to be effective in mouse models is based on raising immunity against the conserved proteins of the influenza virus.…”