Intranasal DNA Vaccination Induces Potent Mucosal and Systemic Immune Responses and Cross-protective Immunity Against Influenza Viruses

Abstract

The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following intranasal administration of luciferase-coding DNA. Using PEI formulation, intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or intranasal immunization with naked-DNA. Furthermore, intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of intranasal DNA as an effective vaccination route.

Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity

“…In particular, microand nano-particle delivery systems that encapsulate protein antigens or DNA that encode for antigens have been evaluated. However, the focus of intranasal vaccination has often been on the treatment of infectious diseases 29,[41][42][43][44][45][46][47] . Nonetheless, a recent study has demonstrated that nanoparticles composed of modified c-polyglutamic acid (c-PGA) encapsulating full length OVA protein instilled intranasally induced anti-tumor immunity against melanoma 48 .…”

Enhanced Immunogenicity of an HIV-1 DNA Vaccine Delivered with Electroporation via Combined Intramuscular and Intradermal Routes

“…Despite the many advantages, most conventional DNA vaccination strategies appear to be poorly immunogenic. Therefore, DNA vaccines have failed to translate from earlier murine studies to humans, leading to poor efficacy in human clinical trials (7,8), and as a consequence, no prophylactic DNA vaccine is clinically approved for use in humans (5). To enhance the immunogenicity of DNA vaccines, strategies such as promoter selection, codon optimization, and different routes of administration have been employed (5).…”

Comparison of single 1-day-old chick vaccination using a Newcastle disease virus vector with a prime/boost vaccination scheme against a highly pathogenic avian influenza H5N1 challenge

“…This indicates that other immune mechanisms in the host must be involved in the rNDV-H5-induced clinical and shedding protection. The induction of a potent virus-specific immune response at the mucosal surfaces, as observed in mice after mucosal administration of a DNA vaccine, was able to reduce the AIV replication in chickens (Torrieri-Dramard et al, 2011). Similarly, in our study, one or two administration(s) of rNDV-H5 induced a high IgG-mediated immunity against NDV in the digestive tract, which could be related to the enterotropic nature of the rNDV-H5 vaccine (Rauw et al, 2009).…”

“…Recent studies have reported that AI protection might not only be correlated with the levels of circulating antibodies (Thomas et al, 2006;Zhong et al, 2010) but also with the cellular immune response, as shown in mice after vaccination with AI inactivated or DNA vaccines (Hovden et al, 2009;Torrieri-Dramard et al, 2011). The present study shows for the first time that NDV and AI-specific CMI could be induced by the rNDV-H5 vaccine.…”