S Afr J Sci.2013 Sep-Oct;109(9-10)

An H5N1 influenza DNA vaccine for South Africa.

Elizabeth Mortimer, Inga I. Hitzeroth (contact author), Amelia Buys, Sandiswa Mbewana, Edward P. Rybicki

 

ABSTRACT:

The highly pathogenic avian influenza virus H5N1 is a potent pandemic threat because of its frequent transmission from birds to humans and the increasing possibility of human to human transmission. During the 2009 H1N1 pandemic it was clear that rapid influenza vaccine production is a problem worldwide. Additionally, developing countries like South Africa generally cannot produce their own influenza vaccines because the traditional egg-based vaccine production method currently employed is too lengthy and too difficult to establish. As part of an exercise aimed at exploring the feasibility of producing emergency response influenza vaccines, we investigated an experimental DNA vaccine to the H5N1 influenza virus. We focused on the virion haemagglutinin, because it elicits the primary neutralising immune response following infection. Accordingly, we developed an H5N1 DNA vaccine with full-length and truncated versions of the haemagglutinin gene, to match previously developed protein candidates. Vaccinated mice developed a strong antibody response to the haemagglutinin protein. In addition, the full-length H5 gene elicited high haemagglutination inhibition titres in mice, indicating that it has potential as a candidate pandemic vaccine for South Africa.

 

SUPPLEMENT:

This study forms part of an initiative in our Biopharming Research Unit at the University of Cape Town to determine if it is possible for South Africa to develop its own rapid-response influenza pandemic vaccines, instead of relying on the goodwill of developed countries and the World Health Organisation (WHO) for vaccine stocks during pandemic outbreaks. Our main focus is to produce rapid-response, cost-effective vaccines, which we explored using various expression systems. So far, haemagglutinin (HA) protein-based candidate subunit vaccines against H5N1 were successfully produced at high yield in tobacco plants (1) and as stable candidate DNA vaccines (2). We have also investigated the development of a universal anti-flu plant-produced vaccine using part of the matrix-2 protein (M2e) (unpublished data).

In the study of Mortimer et al. 2013, two candidate DNA vaccines were produced based on two variants of the H5N1 haemagglutinin, i.e. the full-length membrane-bound form as well as a truncated form lacking the transmembrane region. This truncated form does not insert into the membrane and is soluble under normal conditions. We used the same HA variants from the same H5N1 strain that we used for our candidate plant-produced subunit vaccines (1) in order to have a direct comparison between the various candidate vaccines. Overall, both our plant-produced and DNA candidate vaccines elicited H5-specific antibody responses in mice. However, the candidate DNA vaccines performed better in the gold-standard haemagglutinin inhibition tests than their plant-produced counterparts. All the mice vaccinated with the full length HA as well as 80% of mice inoculated with the truncated HA had higher HI titres than the benchmark value used for indicating probable protection against influenza in humans (1: 40). In both our plant-produced and our DNA produced candidate vaccines, the full length haemagglutinin candidate vaccine proved to be the most immunogenic in mice.

To conclude, we have shown that plant-produced as well as DNA-based vaccines against a highly dangerous form of influenza virus can potentially be produced in South Africa within a matter of weeks after receiving notification of an influenza pandemic. Both platforms are therefore ideal for pandemic influenza vaccine production for South Africa. Such a capacity would also serve as a regional asset for protection of African countries against pandemics, given the highly likely scenario of developed country pandemic vaccine manufacturing output being pre-empted for home country use. Future work will include further investigation production of candidate vaccines for other potentially pandemic influenza strains, using various production methods.

References

1. Mortimer E, Maclean JM, Mbewana S, Buys A, Williamson AL, Hitzeroth II, Rybicki EP 2012 Setting up a platform for plant-based influenza virus vaccine production in South Africa. BMC Biotechnology 12:14. http://dx.doi. org/10.1186/1472-6750-12-14
2. Mortimer E, Hitzeroth II, Buys A, Mbewana S, Rybicki EP 2013 An H5N1 influenza vaccine for South Africa S Afr J Sci. 109: 1-4 (9/10). http://dx.doi.org/10.1590/ sajs.2013/20120053

Acknowledgements

This research was funded by the Poliomyelitis Research Foundation (South Africa). The National Research Foundation (South Africa) provided E.M. with a postdoctoral bursary.

Contact information

Inga Hitzeroth PhD
Senior Research Officer
Biopharming Research Unit
Department of Molecular and Cell Biology
University of Cape Town
South Africa
Tel: +27 21 650 5712
Inga.hitzeroth@uct.ac.za

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