... Magdalina Jancarova, Petr Volf and Matthew Rogers (sand fly saliva, flies); @alainkohlvirology.bsky.social @akiraalexander.bsky.social and Maria Grazia Cusi for TOSV; Sandy Macdonald (RNA-seq analyses); and Kave Shams (co-supervision, clinical insights).


Huge thanks to our brilliant team and collaborators! Not least the talented @yoncakeskekturk.bsky.social who drove this forward with help from @ailishmccafferty.bsky.social, Liam Barningham, and Çağdaş Kaya from VHIT @york.ac.uk @universityofleeds.bsky.social

Finally, we show a heat-stable RNase-sensitive salivary factor boosts infection; if identified could provide a potential target for new antivirals or vaccines
#VectorBiology #Arboviruses #Immunology #Virology #SandFlies #SkinBiology #HostPathogenInteractions

Although macrophages become positive for virus, they did not generate new infectious virus. Instead virus targeted fibroblasts expressing markers typical of a developmentally-primitive state.

Mechanistically, biting/saliva pushes fibroblasts into a primitive, wound-healing-like state; a reprogrammed condition that makes them highly productive for viral replication.

When transmitted at natural sand fly bites/with saliva, infection was more severe:

⬆️ higher viral loads

🔥 stronger inflammation

🧠 neurological signs and connective tissue inflammation

Inclusion of vector saliva profoundly changes disease trajectories.

Sand fly bites/saliva from two genera enhanced infection by both Toscana virus and a genetically unrelated virus (SFV) in a type I interferon independent manner (mouse model).

Sand flies are an important group of biting insects that spread both parasites and viruses, including the neurotropic #Toscana virus. It was not known if the response to sand fly biting altered outcome to infection with virus.

Itch is a complex response involving host neuroimmune and maybe also vector derived factors, which we didn’t assess per se. We did find some inflammatory responses to bites (eg neutrophil signature) were suppressed by vaccination. Suggesting it skewed bite responses to being anti-viral.

Thanks to first author Liam Barningham and our brilliant collaborators at Laboratory of Malaria and Vector Research, @NIH and Center for Vaccine Development and Global Health, UniOfMaryland who did the trial👏
Special shout-out to our colleagues at ConservBio who developed AGSv-PLUS. 6/6

Together, these results show that vaccination reshapes the skin’s bite response.
This could increase resistance to infection, pointing to a novel, vector-based vaccine strategy.
5/6

What we saw 👇
✔️ Bites triggered strong leukocyte recruitment signatures + Th1/CD8⁺ responses (esp. albopictus)
✔️ Adjuvanted AGS-v PLUS boosted antiviral/ISG pathways but dampened neutrophil-driven inflammatory signatures
✔️ NK/DC signatures elevated in some groups
4/6

In a Phase I trial cohort, we sampled skin 48h after controlled Ae. aegypti & Ae. albopictus bites.
We compared placebo vs AGS-v PLUS (±adjuvant) to ask: does vaccination alter the early immune response at the bite site? 3/6

One genus of 🦟 transmits most viruses that cause dengue, Zika, chikungunya, yellow fever.
Most vaccines target the virus and are pathogen-specific.
We asked whether targeting mosquito saliva could reprogram skin immunity at the bite, a universal strategy with pan-viral potential

Why? Is a flapjack something different where you are?