H5N1 Protection by Seasonal Influenza Vaccine in Homologous and Heterologous Prime/Boost Vaccination

Roos A, Roozendaal R, Damman-Riahi S, Vreugdenhil J, Vaneman J, Dekking L, Koldijk M, Goudsmit J and Radošević K

A number of different approaches aimed at broadening the cross-protective ability of seasonal influenza vaccines are being explored today. Priming a seasonal vaccine with three administrations of DNA encoding H1 HA corresponding to the HA in the seasonal vaccine has been shown to confer protection against heterologous H1N1 influenza. Here we evaluated the heterosubtypic protection induced by a seasonal influenza vaccine when primed with H1 HA DNA and, in parallel, when given as a homologous prime/boost regimen.
Balb/c mice were immunized three times with vaccine homologous H1 HA DNA prior to a boost with seasonal influenza vaccine (season 2009/2010; Northern Hemisphere), or immunized three times with the seasonal influenza vaccine. To assess cross-protection, mice were subsequently challenged with either heterologous H1N1 or heterosubtypic H5N1 influenza virus.
The level of heterologous H1N1 protection elicited by the seasonal influenza vaccine was enhanced by priming with H1 HA DNA. In contrast, priming with H1 HA DNA did not enhance the level of heterosubtypic H5N1 protection. The heterologous prime boost regimen showed to be less efficient than multiple immunizations with seasonal vaccine in conferring protection against H5N1. Neither the DNA-priming vaccination regimen, nor the homologous prime/boost regimen induced detectable H5N1 cross-reactive anti-HA or anti-NA antibodies. Homologous prime /boost vaccination did induce higher levels of anti-NP antibodies.
Here we demonstrate that priming a seasonal influenza vaccine with vaccine homologous H1 HA encoding DNA enhances the level of heterologous H1N1 but not heterosubtypic protection induced by the vaccine alone. Homologous prime/boost vaccination resulted in higher levels of heterosubtypic protection. Of the immunogenicity parameters tested for both heterologous and homologous prime/boost regimens only anti-NP responses follow the same pattern as heterosubtypic protection.