Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections

Abstract

Background: Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that gamma-ray inactivated flu virus can induce cross-reactive Tc cell responses.

Methodology/principal finding: Here, we report that intranasal administration of purified gamma-ray inactivated human influenza A virus preparations (gamma-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of gamma-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections.

Conclusions/significance: Intranasal gamma-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.

Figure 1. Cross-reactive cytotoxic T cell responses induced by γ-Flu.

10-week-old BALB/c mice were either infected or vaccinated with live A/PR8, γ-A/PR8, live A/PC, or γ-A/PC. Six days later, splenocytes from these mice were tested for their killing activity against mock, A/PC-, A/PR8-, A/JAP-infected, and NPP-labelled P815 targets. Data represent % specific lysis after 6 h assay time at an effector to target cell ratio of 120∶1.

Figure 2. Intranasal vaccination with γ−Flu provides superior protection to heterotypic virus challenge.

Groups of 10 BALB/c mice were either mock treated (A) or vaccinated with γ−A/PC (3.2×10⁶ PFU equivalents) intravenously (B) or intranasally (C). Mice were challenged intranasally after 3 weeks with a lethal dose (6×10² PFU) of A/PR8 and weight recorded daily for 21 days. Survival (D) of mice mock treated, or vaccinated i.n., i.v., i.p., or s.c. and challenged as for (A–C) and monitored for 21 days.

Figure 3. Intranasal vaccination with γ−Flu (γ−A/PR8[H1N1]) protects against H5N1 challenge.

Groups of 10 BALB/c mice were either mock treated (A) or vaccinated with γ−A/PR8 (B). Mice were challenged 4 weeks later with 3 MID₅₀ of A/Vietnam/1203/2004[H5N1] intranasally and weight recorded daily for 21 days.