A vaccine designed to protect against all mosquito-borne diseases by changing the way our immune system responds to bites has been shown to be safe in a small human trial. The results suggest it should reduce infections by the Zika virus, and also show that mosquitoes that feed on vaccinated people lay fewer eggs.
鈥淭he results are very positive,鈥� says Olga Pleguezuelos at PepTcell, one of the companies involved in developing the vaccine with funding from the UK and US governments.
The hope is that the vaccine could provide protection against all mosquito-borne diseases including Zika, West Nile, chikungunya, dengue, yellow fever and malaria. It might work best when combined with other vaccines targeting these pathogens directly, Pleguezuelos says, but for some of these diseases no vaccines are currently available.
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When a mosquito inserts its proboscis into our skin, it secretes saliva containing a complex mix of proteins that not only stops blood clotting, but also changes our immune response in a way that makes us more likely to be infected by any diseases the mosquito carries.
If you inject malaria parasites into people with a needle, it takes thousands to infect them, Pleguezuelos says. But a mosquito bite that transfers as few as five parasites can infect people.
Together with researchers at the National Institutes of Health in the US, Pleguezuelos has developed a vaccine containing synthetic proteins that match parts of some of the key proteins in mosquito saliva. The aim is to change our immune response to mosquito saliva in a way that reduces infections.
The results of , called AGS-v, were published last year. The trial showed it was safe, but revealed little else, Pleguezuelos says.
Now the team has done another small human trial with a new version of the vaccine containing an extra protein designed to make it effective against a wider range of mosquitoes. This version, called AGS-v PLUS, is also safe, according to results presented at a recent meeting of the .
This time, however, mosquitoes were allowed to feed on some of the volunteers several weeks after vaccination. Aedes aegypti mosquitoes fed on one arm and A. albopictus on the other.
The researchers monitored what happened to the mosquitoes after this. They found those that fed on vaccinated people didn鈥檛 survive as long and laid fewer eggs. This suggests the vaccine could potentially help control mosquito numbers.
The team then tried to recreate in the lab what was happening at the bite site by exposing samples from volunteers to the Zika virus. With the samples from vaccinated people, there was a reduction in infectiousness of the virus, as measured by how many cells it subsequently infected.
鈥淓ven though we are not targeting the pathogen itself, by your immune system recognising the saliva in the way we are training it to, it creates a hostile environment for the virus,鈥� says Pleguezuelos. 鈥淲hen we saw there was a significant difference, it was great news for us.鈥�
Whether this will greatly reduce infections in the real world remains to be seen. The next step will be to carry out so-called challenge trials, Pleguezuelos says. This means deliberately trying to infect volunteers by exposing them to mosquitoes carrying various diseases.
鈥淚 for one think this is exciting and look forward to larger trials,鈥� says at Upstate Medical University in Syracuse. 鈥淚t鈥檚 an approach worth exploring.鈥�
There is growing evidence that salivary proteins not only increase the risk of being infected in the first place, but can also make the resulting disease more severe, he says.
Other groups are already working on vaccines targeting the saliva of other biting animals that spread diseases, such as the ticks that carry Lyme disease and the sandflies that carry leishmaniasis.
