DNA vaccine based on conserved HA-peptides induces strong immune response and rapidly clears influenza virus infection from vaccinated pigs

Abstract

Swine influenza virus (SIVs) infections cause a significant economic impact to the pork industry. Moreover, pigs may act as mixing vessel favoring genome reassortment of diverse influenza viruses. Such an example is the pandemic H1N1 (pH1N1) virus that appeared in 2009, harboring a combination of gene segments from avian, pig and human lineages, which rapidly reached pandemic proportions. In order to confront and prevent these possible emergences as well as antigenic drift phenomena, vaccination remains of vital importance. The present work aimed to evaluate a new DNA influenza vaccine based on distinct conserved HA-peptides fused with flagellin and applied together with Diluvac Forte as adjuvant using a needle-free device (IntraDermal Application of Liquids, IDAL®). Two experimental pig studies were performed to test DNA-vaccine efficacy against SIVs in pigs. In the first experiment, SIV-seronegative pigs were vaccinated with VC4-flagellin DNA and intranasally challenged with a pH1N1. In the second study, VC4-flagellin DNA vaccine was employed in SIV-seropositive animals and challenged intranasally with an H3N2 SIV-isolate. Both experiments demonstrated a reduction in the viral shedding after challenge, suggesting vaccine efficacy against both the H1 and H3 influenza virus subtypes. In addition, the results proved that maternally derived antibodies (MDA) did not constitute an obstacle to the vaccine approach used. Moreover, elevated titers in antibodies both against H1 and H3 proteins in serum and in bronchoalveolar lavage fluids (BALFs) was detected in the vaccinated animals along with a markedly increased mucosal IgA response. Additionally, vaccinated animals developed stronger neutralizing antibodies in BALFs and higher inhibiting hemagglutination titers in sera against both the pH1N1 and H3N2 influenza viruses compared to unvaccinated, challenged-pigs. It is proposed that the described DNA-vaccine formulation could potentially be used as a multivalent vaccine against SIV infections.

Influenza A Virus in Swine: Epidemiology, Challenges and Vaccination Strategies

“…DNA vaccines based on different gene combinations (mainly HA) demonstrated good degrees of protection against homologous challenge (70,71,(97)(98)(99). Needle-free and IM delivery methods were tested to be successful, but recent studies evaluated needlefree delivery as it was claimed to be safer and easier to administer for large scale vaccination (97)(98)(99). The combination of priming with a DNA vaccine and boosting with an inactivated vaccine conferred significantly better protection than only two doses of DNA vaccine (71).…”

“…The combination of priming with a DNA vaccine and boosting with an inactivated vaccine conferred significantly better protection than only two doses of DNA vaccine (71). However, heterologous cross protection was demonstrated even in presence of MDAs after two doses of DNA vaccine (99). The major handicap of those vaccines is that large doses of DNA and several vaccination doses were required to confer protection.…”

Future perspectives on swine viral vaccines: where are we headed?

“…In a subsequent challenge study, the vaccine was found to induce broad protection against heterologous PRRSV strains when administered twice to pigs [ 88 ]. In addition, a DNA vaccine based on conserved haemagglutinin (HA) peptides fused with flagellin, administered with a needle-free device, induced a strong immune response and rapidly cleared IAV from vaccinated pigs [ 89 ]. Maternally derived antibodies did not interfere with vaccination and there was a markedly increased mucosal IgA response in vaccinated pigs compared to non-vaccinated pigs [ 89 ].…”

“…Especially for intradermal applications, the dermis is an excellent site for vaccine delivery and rich in dendritic cells as well as lymph vessels which promote fast processing of incoming antigen ( http://www.positiveaction.info/pdfs/stars/pt_MSD1-8.pdf ). DNA vaccines appear to benefit from the intradermal route of administration [ 87 , 89 ]. Several commercial health companies have started to produce their own, individual intradermal injection devices, which can be used on company-specific vaccine bottles, and are sold to producers as package deals.…”

The Key Role of Nucleic Acid Vaccines for One Health

“…The version of a broad influenza DNA vaccine for production pigs may induce mostly antibodies (against HA and/or NA) to prevent infection and spread by shedding of influenza virus. In contrast, the version for humans should also contain genes for conserved internal virus proteins for additional CMI induction (against M and/or NP) to protect humans from disease and death, as well [ 66 , 86 , 87 ], and to provide potential cross-strain protection against newly arising drifted and shifted strains [ 5 ].…”