A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection

Author:

Babapoor Sankhiros1,Neef Tobias23,Mittelholzer Christian45,Girshick Theodore6,Garmendia Antonio1,Shang Hongwei7,Khan Mazhar I.1,Burkhard Peter23

Affiliation:

1. Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06268, USA

2. Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, Storrs, CT 06269, USA

3. The Institute of Materials Science, University of Connecticut, 97 North Eagleville Road, Storrs, CT 06269, USA

4. M.E. Müller Institute, University of Basel, 50/70 Klingelbergstrasse, 4056 Basel, Switzerland

5. Institute for Medical Microbiology, University of Basel, 4003 Basel, Switzerland

6. Charles River SPAFAS, Inc., 106 RT 32 North Franklin, Storrs, CT 06254, USA

7. Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, CT 06269, USA

Abstract

Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (P<0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.

Funder

U.S. Department of Agriculture

Publisher

Hindawi Limited

Subject

Virology,Infectious Diseases,Epidemiology

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