» Articles » PMID: 23658445

A Novel Bivalent Vaccine Based on a PB2-knockout Influenza Virus Protects Mice from Pandemic H1N1 and Highly Pathogenic H5N1 Virus Challenges

Overview
Journal J Virol
Date 2013 May 10
PMID 23658445
Citations 14
Authors
Affiliations
Soon will be listed here.
Abstract

Vaccination is an effective means to protect against influenza virus. Although inactivated and live-attenuated vaccines are currently available, each vaccine has disadvantages (e.g., immunogenicity and safety issues). To overcome these problems, we previously developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2 protein-expressing cells. Here, we generated two PB2-KO viruses whose PB2-coding regions were replaced with the HA genes of either A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1). The resultant viruses comparably, or in some cases more efficiently, induced virus-specific antibodies in the serum, nasal wash, and bronchoalveolar lavage fluid of mice relative to a conventional formalin-inactivated vaccine. Furthermore, mice immunized with these PB2-KO viruses were protected from lethal challenges with not only the backbone virus strain but also strains from which their foreign HAs originated, indicating that PB2-KO viruses with antigenically different HAs could serve as bivalent influenza vaccines.

Citing Articles

Generation and Characterization of Single-Cycle Infectious Canine Influenza A Virus (sciCIV) and Its Use as Vaccine Platform.

Nogales A, Chiem K, Breen M, DeDiego M, Parrish C, Martinez-Sobrido L Methods Mol Biol. 2022; 2465:227-255.

PMID: 35118625 DOI: 10.1007/978-1-0716-2168-4_13.


Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines.

Rodriguez L, Blanco-Lobo P, Reilly E, Maehigashi T, Nogales A, Smith A Viruses. 2019; 11(10).

PMID: 31658679 PMC: 6832241. DOI: 10.3390/v11100928.


The Quest for a Truly Universal Influenza Vaccine.

Jang Y, Seong B Front Cell Infect Microbiol. 2019; 9:344.

PMID: 31649895 PMC: 6795694. DOI: 10.3389/fcimb.2019.00344.


Novel Approaches for The Development of Live Attenuated Influenza Vaccines.

Blanco-Lobo P, Nogales A, Rodriguez L, Martinez-Sobrido L Viruses. 2019; 11(2).

PMID: 30813325 PMC: 6409754. DOI: 10.3390/v11020190.


Pregnancy and infection: using disease pathogenesis to inform vaccine strategy.

Vermillion M, Klein S NPJ Vaccines. 2018; 3:6.

PMID: 29423318 PMC: 5794984. DOI: 10.1038/s41541-017-0042-4.


References
1.
Rimmelzwaan G, Fouchier R, Osterhaus A . Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a basis for vaccine development. Curr Opin Biotechnol. 2007; 18(6):529-36. DOI: 10.1016/j.copbio.2007.11.002. View

2.
Yamada S, Hatta M, Staker B, Watanabe S, Imai M, Shinya K . Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog. 2010; 6(8):e1001034. PMC: 2916879. DOI: 10.1371/journal.ppat.1001034. View

3.
Sakabe S, Ozawa M, Takano R, Iwastuki-Horimoto K, Kawaoka Y . Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice. Virus Res. 2011; 158(1-2):124-9. PMC: 3103651. DOI: 10.1016/j.virusres.2011.03.022. View

4.
Benton K, Misplon J, Lo C, Brutkiewicz R, Prasad S, Epstein S . Heterosubtypic immunity to influenza A virus in mice lacking IgA, all Ig, NKT cells, or gamma delta T cells. J Immunol. 2001; 166(12):7437-45. DOI: 10.4049/jimmunol.166.12.7437. View

5.
Lambert L, Fauci A . Influenza vaccines for the future. N Engl J Med. 2010; 363(21):2036-44. DOI: 10.1056/NEJMra1002842. View