Heterologous HA DNA vaccine prime—inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses

Abstract

The trivalent inactivated vaccine (TIV) is used to prevent seasonal influenza virus infection in humans, however, the immunogenicity of this vaccine may be influenced by the priming effect of previous influenza vaccinations or exposure to antigenically-related influenza viruses. The current study examines the immunogenicity of a clinically licensed TIV in rabbits naïve to influenza antigens. Animals were immunized with either the licensed TIV, a bivalent (H1 and H3) HA DNA vaccine or the combination of both. Temporal and peak level serum anti-influenza virus IgG responses were determined by ELISA. Functional antibody responses were measured by hemagglutination inhibition and microneutralization against either A/NewCaledonia//20/99 (H1N1) or A/Panama/2007/99 (H3N2) influenza viruses. Our results demonstrate that the immunogenicity of the TIV is low in seronegative animals. More significantly, the heterologous DNA prime-TIV boost regimen was more immunogenic than the homologous prime-boost using either TIV or DNA vaccines alone. This finding justifies further investigation of HA DNA vaccines as a priming immunogen for the next generation of vaccines against seasonal or pandemic influenza virus infections.

Immunogenicity of DNA vaccines in humans: It takes two to tango

“…Recently in a small animal model, we demonstrated that a HA DNA prime plus an inactivated flu vaccine boost is more effective than using either HA DNA or an inactivated flu vaccine alone in eliciting significantly higher levels of protective antibody responses against influenza infection. 27 For subunit protein-based vaccines, not only are multiple immunizations required to elicit a significant immune response but typically, the use of a strong adjuvant is also needed. It will be interesting to examine whether a DNA priming step can minimize the need for a strong adjuvant or if it can reduce the number and/or dose of subunit vaccinations needed in order to elicit a full scale antibody response.…”

Protective efficacy of a prime-boost protocol using H5-DNA plasmid as prime and inactivated H5N2 vaccine as the booster against the Egyptian avian influenza challenge virus

“…Results of the present study demonstrate that a prime-boost regimen using pcDNA3.1D/HA1 purified recombinant plasmid with the inactivated H5N2 vaccine is more immunogenic than the use of either pcDNA3.1D/HA1 purified recombinant plasmid or inactivated H5N2 vaccine alone. There is evidence that DNA vaccine is effective in inducing a long lasting B-cell memory (Wang et al, 2008). Others have suggested that the low-dose antigen delivery is more effective in the induction of better antibody response and B-cell memory (Gonzalez-Fernandez and Milstein, 1998;Nichol, 2003).…”

Optimal designs of an HA-based DNA vaccine against H7 subtype influenza viruses

“…11,15,[24][25][26] Furthermore, DNA vaccines have been studied extensively in animals and in clinical trials to optimize a wide range of key parameters including antigen design, dosing, adjuvants, optimal routes of delivery (needle injection, gene gun, and electroporation), and novel immunization regimens, including heterologous primeboost vaccination. 16,[27][28][29][30] Although ferrets are often used as a challenge model to test the protective efficacy of the influenza vaccine, in the current study, our goal is to optimize the DNA vaccine design to enhance its immunogenicity using a less costly animal model. Rabbit was used as the animal model to examine immunogenicity of H7 DNA vaccines because rabbit is highly immunogenic in producing high titer antibody responses and has been widely used for evaluation of vaccine immunogenicity.…”