Influenza vaccines

Abstract

Described herein are vaccines and the use of naked DNA and / or RNA encoding hemagglutinin (HA) from pandemic influenza, e.g., the 1918 H1N1 and / or the 1957 H2N2 and / or the 1968 H3N2 influenza A virus, as a vaccine component against present day and coming H1, H2, H3, H5, N1, N2 containing influenza A infections in humans and swine optionally with the naked DNA and / or RNA encoding Neuraminidase (NA) and / or matrix protein (M) and / or the nucleoprotein (NP) from pandemic influenza virus included. If the vaccine components are used as DNA or RNA vaccines with or without the corresponding protein, the codons can optionally be “humanized” using preferred codons from highly expressed mammalian genes and the administration of this DNA vaccine can be by saline or buffered saline injection of naked DNA or RNA, or injection of DNA plasmid or linear gene expressing DNA fragments coupled to particles. Addition of the matrix protein (M) and / or the nucleoprotein (NP) from the 1918 influenza strain is also disclosed.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit under 35 USC 119(e) of U.S. Patent Application No. 60 / 934,117, filed Jun. 11, 2007.BACKGROUND OF THE INVENTION[0002]The invention concerns therapeutic and prophylactic vaccines for humans and swine, for influenza A infections in humans and swine.[0003]Influenza is one of the oldest and most common diseases known to man, causing between three and five million cases of severe illness and between 250,000 and 500,000 deaths every year around the world. Also, swine are susceptible to human and avian influenza virus, since they possess both receptors in their respiratory tract. Because swine get infection and pneumonia from human influenza strains, they may serve as a dangerous mixing vessel for the generation of new recombinant influenza strains with pandemic potential.[0004]Influenza rapidly spreads in seasonal epidemics affecting 5-15% of the population and the burden on health care costs and lost productiv...

AI Technical Summary

Benefits of technology

[0025]The data herein demonstrates that gene gun administrated codon optimised DNA vaccine in plasmid encoding HA and NA with or without M and NP based on the H1N1 pandemic virus from 1918 induced protection in ferrets against infection with a H1N1 (A / New Caledonia / 20 / 99(H1N1)) present day virus. The circulating H1N1 strain in Europe in the 2006-2007 seasons is New Caledonia-like. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein. By comparison, a similar DNA vaccine encoding the HA and NA of (A / New Caledonia / 20 / 99 (H1N1)) induced less protection. These results suggest not only a unique ability of the DNA vaccines but also a unique and unexpected feature of the 1918 HA and / or NA in inducing especially broad and efficient protective immunity against even extremely drifted strain variants.

[0027]The results surprisingly show that the 1918 H1N1 DNA vaccines are as good as or better candidates for influenza prophylaxis than annual conventional protein based vaccines which frequently need to be updated to match the circulating influenza virus. DNA vaccination induces broader cross-reactivity against drifted strain and longer memory responses. It has been shown that a similar DNA vaccine may protect against the 1918 H1N1 recombinant strain (16). However, the results herein then suggest that the synthetic DNA vaccine based on the 1918 H1N1 sequences protects against extreme drifted variants represented by recent contemporary or seasonal circulating H1N1 strains. Thus it is likely that the suggested 1918 H1N1 DNA vaccine protects against H1N1 strains circulating for up to 89 years and therefore likely also future H1N1 variants. This is highly unexpected since traditional protein split vaccines only protects against the strain it is designed from and thus has to be produced from the actual circulating H1N1 strains sometimes as frequent as every year. Thus, a DNA vaccine encoding the HA and NA of 1918 H1N1 was not expected to protect against such a divergent strain as the present day H1N1, but it does.

Problems solved by technology

Also, swine are susceptible to human and avian influenza virus, since they possess both receptors in their respiratory tract.

Because swine get infection and pneumonia from human influenza strains, they may serve as a dangerous mixing vessel for the generation of new recombinant influenza strains with pandemic potential.

Influenza rapidly spreads in seasonal epidemics affecting 5-15% of the population and the burden on health care costs and lost productivity are extensive (World Health Organization (WHO)).

Moreover, the traditional influenza protein vaccines only have a limited protective effect.

However, in temperate climates it is a winter disease, probably because people come together and stay in less ventilated rooms due to the cold weather.

However, there is consideration disagreement about the actual origin of the virus and many still believe that also this 1918 pandemic strain is a reassortant between a mammalian and avian virus most likely occurring from swine.

The reassortant might be catastrophic if the virus is capable of efficient replication in the new host.

In the worst case, such a reasserted strain might lead to a pandemic, world-spanning infection to which there is no pre-existing immunity in the human population.

Whole inactivated influenza vaccine is not currently used due to high levels of side effects.

The protective effect of the traditional protein split vaccine is very limited and because of the continuous evolution of influenza A virus strains and the type specific antibodies induced by the conventional vaccines, a new vaccine has to be produced every year based on the most recent circulating influenza A strain.

Egg production is too slow (6-12 months) in the case of emerging strains.

If this strain is also an AIV virus highly pathogenic (HP) for poultry, egg production might be impossible because the virus kills the egg embryo.

Also the availability of eggs might be limited and slow down vaccine production.

In the case of no pre-existing immunity in the population, two vaccinations would be necessary, thereby further delaying the vaccine production.

Even if there are no new pandemic influenza A among humans but only spread of a HPV AIV among poultry, a shortage of eggs will limit production of traditional seasonal influenza vaccines on eggs.

In addition, traditional influenza protein vaccines do not have optimal protection as prophylaxis and no therapeutic effect.

The great success with DNA vaccines observed for the murine model for first generation DNA vaccines did not translate well to humans; nonetheless, researchers have recently demonstrated protective antibodies levels by a single dose of gene gun administrated HA DNA vaccine to humans.

This type of response is ineffective against drifted virus variants and therefore the virus composition of the seasonal influenza vaccine has to be assessed every season.

However, cellular immunity alone cannot protect against infection since this requires antibodies.

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