DNA Vaccine Expressing Conserved Influenza Virus Proteins Protective Against H5N1 Challenge Infection in Mice

Abstract

Influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. If an unexpected strain, as in the 1997 H5N1 Hong Kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. Therefore, strategies based on conserved influenza antigens should be explored. We studied DNA vaccination in mice with plasmids expressing conserved nucleoprotein (NP) and matrix (M) from an H1N1 virus. After vaccination, mice were challenged with A/H5N1 viruses of low, intermediate, and high lethality. A/NP+A/M DNA vaccination reduced replication of A/Hong Kong/486/97 (HK/486), a nonlethal H5N1 strain, and protected against lethal challenge with more virulent A/Hong Kong/156/97 (HK/156). After HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone protected poorly against this highly virulent strain. In the absence of antigenically matched hemagglutinin-based vaccines, DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus.

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1

“…Thus, a number of investigators have focused on conserved internal viral proteins NP and M1. 1,[7][8][9][10] In particular, a recent study provided evidence of the significant heterosubtypic protection potential of a DNA ⁄ adenovirus combination expressing NP protein. 1 Internal proteins are conserved among influenza A strains with maximum amino acid differences of 10.8% for NP and 24.6% for M1.…”

“…7,[13][14][15][16] There are conflicting reports as to whether an immune response against NP, M1 and M2 proteins is protective against experimental influenza infection in mice, although most of the experiments involving NP were at least partially successful. 1,[7][8][9][10][13][14][15][16][17][18][19] There has not been a bona fide attempt to investigate the possible benefits of vaccination with NS1 with the exception of a study in which plasmids carrying viral genes were tested separately. 18 NS1 was eliminated early in favour of HA, NA and NP, which in turn provided strain-specific protection based mostly on the humoral antibody response.…”

Oral vaccination with a liposome‐encapsulated influenza DNA vaccine protects mice against respiratory challenge infection

“…It became clear that cell-mediated immunity has a more important role in inhibiting viral replication and clearance of influenza virus infection [Epstein et al, 2000]. Genetic vaccination using influenza DNA vaccine better introduced the antigen-specific CTL and IFN-g production in comparison to skinmediated vaccination [Epstein et al, 2000[Epstein et al, , 2002Wang et al, 2003]. Data presented in this article also show that oral vaccination with liposome-encapsulated pcDNA3.1(þ)/M1 DNA vaccine can induce antigen-specific cytotoxicity very well.…”

“…In addition, vaccines using conserved components of influenza A virus, such as nucleoprotein (NP) or matrix protein (M), can induce protection against many influenza A strains, including those of divergent subtypes [Epstein et al, 2000;Ozaki et al, 2005;Zhirnov et al, 2007]. It was clear that DNA constructs expressing NP and M proteins induce antigen-specific antibodies and T-cell responses, and protect mice against both homologous and heterologous influenza virus challenge [Epstein et al, 2002;Heinen et al, 2002].…”

Mucosal Immunization with a Candidate Universal Influenza Vaccine Reduces Virus Transmission in a Mouse Model

“…Virus titers in lung tissues and nasal wash samples were determined by a TCID 50 assay on MDCK cells (29), read out by hemagglutination with 0.5% chicken erythrocytes as described previously (6). Titers were calculated by using the method of moving averages and Weil's tables (30,31).…”