DNA and protein-generated chimeric molecules for delivery of influenza viral epitopes in mouse and humanized NSG transfer models

ABSTRACT

Purified subunit viral antigens are weakly immunogenic and stimulate only the antibody but not the T cell-mediated immune response. An alternative approach to inducing protective immunity with small viral peptides may be the targeting of viral epitopes to immunocompetent cells by DNA and protein-engineered vaccines. This review will focus on DNA and protein-generated chimeric molecules carrying engineered fragments specific for activating cell surface co-receptors for inducing protective antiviral immunity. Adjuvanted protein-based vaccine or DNA constructs encoding simultaneously T- and B-cell peptide epitopes from influenza viral hemagglutinin, and scFvs specific for costimulatory immune cell receptors may induce a significant increase of anti-influenza antibody levels and strong CTL activity against virus-infected cells in a manner that mimics the natural infection. Here we summarize the development of several DNA and protein chimeric constructs carrying influenza virus HA317–41 fragment. The generated engineered molecules were used for immunization in intact murine and experimentally humanized NSG mouse models.

KEYWORDS:

• DNA vaccines
• engineered antibodies
• influenza virus
• chimeric molecules

Acknowledgments

We thank Polia Marinova (American College of Sofia, Bulgaria) for the helpful discussions and ideas.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by grant DTK 02/19 from the National Science Fund, Bulgaria, and ACTIONS CONCERTEES INTERPASTEURIENNES, France (all to A. Tchorbanov) and the European Fund for regional development through Operational Program Science and Education for Smart Growth 2014–2020, Grant BG05M2OP001-1.002-0001-C04 “Fundamental Translational and Clinical Investigations on Infections and Immunity”.