ViroBlogy

Rift valley fever virions: Linda Stannard, UCT

It was an interesting week, what with a Rift valley fever virus (RVFV) outbreak in South Africa associated with two human deaths – and an excellent journal club presentation (thanks, Liezl!) on a new candidate virus-like particle vaccine made in insect cells.  RFV was in fact worked on in the 1960s at UCT in the old Virus Research Unit under the legendary Dr Alfred Polson at the then Medical School (see pictures link here) – and a couple of folk even got infected while trying to purify it, but we won’t speak of that.

First, the news:

Health-e (Cape Town)

South Africa: Rift Valley Fever Update – a Total of 21 Cases Have Been Confirmed

15 March 2010  press release

The following is a statement by [South African] Deputy Minister of Health Dr Molefi Sefularo, MP, pertaining to the recent deaths from Rift Valley Fever in South Africa.

As of 15 March 2010, a total of 21 human laboratory confirmed cases of River [sic] Valley Fever (RVF) have been confirmed – all acquired in Free State – with two deaths. This brings a total to 22 human cases of RVF – with one in Northern Cape.

Most of these cases reported direct contact with RVF-infected livestock and or linked to farms with confirmed animal cases of RVF. The human cases are; farmers, veterinarians and farm workers. Additional suspect cases are currently being tested.

…
While there is no specific treatment, the majority of persons affected will recover completely. People should avoid contact with the tissues of infected animals, refrain from drinking unpasteurised milk and prevent mosquito bites to avoid becoming infected. Farmers and veterinarians should wear protective clothing when handling sick animals or their tissues. There is no routine vaccine available for humans.

…
Rift Valley Fever (RVF) is a viral disease that can cause severe disease in a low proportion of infected humans.

The virus is transmitted by mosquitoes and causes outbreaks of abortion and deaths of young livestock (sheep, goats and cattle). Humans become infected from contact with infected tissues of livestock and less frequently from mosquito bites. In sub-Saharan Africa the mosquitoes which transmit the virus do not enter human dwellings but feed on livestock outdoors at night. The disease occurs throughout Africa and Madagascar when exceptionally heavy rains favour the breeding of the mosquito vectors.

Clinical features in humans

Typically illness is asymptomatic or mild in the vast majority of infected persons, and severe disease would be expected to occur in less than 1% of infected persons.

Key symptoms:

The incubation period (interval from infection to onset of symptoms) for RVF varies from two to six days.

• Sudden onset of flu-like fever and/or muscle pain.
• Some patients develop neck stiffness, sensitivity to light, loss of appetite and vomiting.

Symptoms of RVF usually last from four to seven days, after which time the immune response becomes detectable with the appearance of antibodies and the virus gradually disappears from the blood.

Severe form of RVF in humans includes:

• Vision disturbances
• Intense headache, loss of memory, hallucinations, confusion, disorientation, vertigo, convulsions, lethargy and coma and;
• Haemorrhagic Fever [rarely – Ed.]

The public living in the affected areas is encouraged to seek medical attention at their nearest Health facilities, should they have any of the above symptoms.

This is an unusual outbreak, because these normally occur only in high summer rainfall regions near the tropics, on the African east coast – and not far inland in essentially arid distinctly sub-tropical areas, like the Free State and Northern Cape.

However, there is news at hand that may be of use in the future: while there is currently no human vaccine, and veterinary vaccines are apparently so attenuated as to require several applications to be effective, SM de Boer and colleagues in The Netherlands claim that subunit VLP vaccines derived by envelope glycoprotein expression in insect cells appear to confer complete protection in vaccinated animals.

Vaccine. 2010 Mar 8;28(11):2330-9. Epub 2010 Jan 5.

Rift Valley fever virus subunit vaccines confer complete protection against a lethal virus challenge.

de Boer SM, Kortekaas J, Antonis AF, Kant J, van Oploo JL, Rottier PJ, Moormann RJ, Bosch BJ.

“Here we report the evaluation of two vaccine candidates based on the viral Gn and Gc envelope glycoproteins, both produced in a Drosophila insect cell expression system. Virus-like particles (VLPs) were generated by merely expressing the Gn and Gc glycoproteins. In addition, a soluble form of the Gn ectodomain was expressed and affinity-purified from the insect cell culture supernatant. Both vaccine candidates fully protected mice from a lethal challenge with RVFV. Importantly, absence of the nucleocapsid protein in either vaccine candidate facilitates the differentiation between infected and vaccinated animals using a commercial recombinant nucleocapsid protein-based indirect ELISA”.

Great accomplishments; great paper – and I note that if you can do it in insect cells, you can do it in plants…just like influenza viruses.

Because, as de Boer et al. state in their Introduction:

“Although the overall case-fatality rate is estimated at 0.5–1.0%, recent outbreaks show considerably higher numbers. The high case-fatality rates combined with the potential of rapid spread via its vector explains the recognition of RVFV as a potential bioterrorism agent by the United States government. Given the impact of RVF outbreaks on livestock, the human population, and the economy, there is an urgent need for a safe and effective vaccine.” [my emphases]

And one backed by the US Government – which used to work on it as a bioterror agent, according to Wikipedia.  Ah, well: some day they’ll just want to do it because it’s the humanitarian thing to do.  Like now, possibly: DARPA is funding Fraunhofer USA to the tune of $4.4 million to make H1N1 vaccines in plants, following their successes over the last couple of years in especially transiently expressing HA proteins.

Going green: the sensible thing to do.