Mosquito-borne viral diseases place an enormous and growing burden on health systems worldwide. Dengue alone causes an estimated 390 million infections each year, and close to half the world's population now lives in at-risk areas.
The year 2024 marked a record year for reported cases. Chikungunya has also seen a sharp resurgence, with over 500,000 cases and 186 deaths reported across more than 40 countries in 2025. Aedes aegypti and Aedes albopictus, the key mosquito species responsible for transmitting these and other arboviruses such as Zika virus, are now found on every continent except Antarctica, and unpredictable outbreaks continue to occur despite large-scale vector control and prevention efforts.
Conventional vaccines target specific pathogens, but a newer strategy that targets the vector for arthropod-borne diseases is proposed. Vaccines built from mosquito antigens, drawn from either the salivary glands or the midgut, can train the immune system to block transmission before infection even takes hold, regardless of which virus the mosquito happens to be carrying. This approach has the advantage of remaining effective across multiple pathogens and strains, including drug-resistant pathogens.
It’s not about targeting each virus separately but targeting the vector. And this is what Iso Lomso fellow Robert Adamu Shey of the Department of Biochemistry & Molecular Biology at the University of Buea, Cameroon, hopes to develop.
Shey explained that 6.4 billion people are at risk globally of at least one vector-borne disease, which constitutes 17% of infectious diseases. In addition, about one billion are infected annually, with approximately 1 million deaths. For arboviruses (viruses transmitted by arthropods such as mosquitoes or ticks), about 5.6 billion people are at risk per year, with more than 390 million annual infections, and over 700 000 deaths. There are about 500 arboviruses, of which 150 cause human diseases. “Africa carries a huge burden with more outbreaks and spread into new regions, placing an increasing strain on already-overworked health systems,” said Shey.
“Mosquitoes specifically are the world’s deadliest animal – causing more than one million deaths per year,” he added. “Aedes aegypti and Aedes albopictus cause Yellow Fever, Dengue, Chikungunya, Zika, West Nile and Rift Valley disease, with transmission of at least one virus currently ongoing on every continent, except Antarctica.”
A global village
Historically, these diseases have disproportionately affected poorer people and regions, but there is now a growing burden in more affluent countries and areas where they have never been seen before.
“There are now expanding vector habitats due to globalisation and increasingly rapid, unplanned urbanisation,” he explained. “Mosquitoes are moving closer to people. The world is a global village which is mostly a good thing but not when it comes to mosquitoes.”
He explained that warmer, wetter conditions due to changing climates push the vector to new latitudes and altitudes previously unsuitable for transmission. Dense cities with standing water and poor waste management create ideal breeding sites close to human populations, and increased global travel means increased transmission and more frequent outbreaks.
“They are being detected in areas where they were never seen before.” (Ironically, this could eventually help the research-funding landscape as these diseases occur in wealthier regions.)
Existing control measures include the use of chemical insecticides and larvicides; habitat and source reduction through removing water sources and improving waste management; and personal-protection measures and community-engagement campaigns. “However, all these measures reduce exposure but don’t eliminate transmission, and their effectiveness fades fast,” said Shey.
Biological control is also possible via releasing Wolbachia-infected mosquitoes. This suppresses viral replication and reproductive capacity, which can reduce local virus transmission. Sterile insect techniques are also used to target males and limit reproduction. However, this approach is funding- and logistics-intensive, requiring sustained-release programmes and therefore difficult to scale, especially for mobile populations.
“So, these existing tools are failing with increased insecticide resistance, sustainability issues, and public compliance all problematic.”
For Yellow Fever, there is a strain-specific, single-dose, live-attenuated vaccine, but it can cause invasive disease, and supply is a big issue. For Dengue, the existing vaccine is restricted to those who have had prior infection, there’s uneven protection across distinct serotypes, and there is a risk of disease in dengue-naïve recipients. Zika and Chikungunya have no widely deployed vaccines.
Changing the target
“There are viral-mutation problems, serotype problems and safety concerns, and new strains of these viruses emerge faster than vaccines can be developed,” said Shey. “So, why not target the vector instead of the viruses? The aim would be to achieve a single vaccine platform with broad-spectrum protection capacity, stopping multiple viruses.”
The evaluation of an Anopheles-based midgut candidate against P. falciparum (the causative agent of malaria) in a human clinical trial in 2023 established that the anti-vector approach is clinically viable. Another vaccine based on Anopheles salivary gland proteins has also been tested, with demonstrated safety.
Shey explained that most vector-based vaccine approaches are looking at either mosquito salivary proteins or midgut antigens. “Salivary antigens modulate the host’s local immune response at the bite site, and midgut antigens support viral replication inside the mosquito. We hope to get to a vaccine that can neutralise the virus where it is established before it infects and then reduce establishment in the vector, thus reducing onward transmission. The hope is that by targeting saliva and midgut proteins, you will block pathogen development and the bite itself ahead of any specific virus.”
“The idea is to protect from within the mosquito and the site of exposure, not just from the pathogen that happens to arrive there,” he said. “Additional advantages of vector-based vaccines are that they can impact mosquito survival and fecundity, can retain efficacy against resistant pathogens, and recombinant protein antigens can be produced at large scale using insect cells.”
Shey’s project is therefore focused on designing and testing two multi-epitope vaccine candidates (Ae-TB-MEV-1 and Ae-TB-MEV-2) which are based on Aedes salivary gland and midgut proteins. “We are using epitopes, not entire proteins, to reduce safety concerns while delivering a robust approach to target specific immune responses,” he said. He explained in detail the development of the two candidates for which they have designed initial constructs. These went to a laboratory for expression, but thus far they have not been able to express enough for testing.
With the challenges faced in expressing the multi-epitope vaccines, he also shared a proposal on the development of virus-like particle (VLP)-based vaccines based on two Aedes salivary-gland proteins (NeSt1 and AgBR1). “VLPs present a platform on which antigens can be safely delivered to the immune system on a highly immunogenic scaffold. VLPs are also more stable at different temperatures, which is important for the cold chain for vaccines in many countries.”
“The antigens selected for the VLP-based studies have shown promising results in preclinical studies,” he said. “There are good antibody titres in mice and increased survival with Zika-challenge testing. But we need to do very good characterisation before human testing.” And so, part of the project will involve an in-depth computer-based characterisation of both antigens.
Looking ahead, Shey highlighted some of the challenges the vector-antigen-based vaccines can face as a control tool against arboviruses in Africa, he said: “Safety is, of course, a big concern, especially with antigens coming from mosquitoes. Also, we will need to show efficacy, not just in mice but also in humans. And it’s also clear that the regulatory pathways will be more complex for vector-based vaccines because the regulatory boards are not as versed in this approach.”
“Vector vaccines won’t replace existing tools but could offer complementary broad protection that is durable against viral evolution. Mosquitoes often carry more than one virus – the hope is that a vector- -based vaccine could protect against multiple viruses by limiting viral replication in mosquitoes. It’s a genuinely novel strategy to mitigate the health impact of arboviruses and offer sustainable solutions.”
Article: Michelle Galloway
Picture: Curt Ruiters, Quickclick Productions