8/ Truly an amazing team to work with. Brilliant science, (and laughs) all the way through 😂🧪”

Congrats agains to @raiannafantin.bsky.social (brilliant first author) and the @camilahcoelho.bsky.social !

7/ Together, our findings establish A35 as a critical therapeutic target for mpox and related orthopoxviruses, paving the way for next-generation antibody therapies and improved vaccines.

6/ Importantly, current smallpox/mpox vaccines (Dryvax, JYNNEOS) elicit low levels of antibodies against these protective A35 epitopes, underscoring a gap in current vaccine design.

5/ Human cohort data showed that convalescent mpox patients naturally generate A35-targeting antibodies. Higher levels of these antibodies correlated with:

• Faster symptom resolution
• Shorter illness
• No hospitalizations

4/ Structural studies revealed all 3 mAbs target a highly conserved epitope in the A35 dimer groove, shared across orthopoxviruses. This explains their breadth and potency.

3/ These A35-specific mAbs:

• Block viral spread in vitro
• Protect mice from lethal mpox & vaccinia infection
• Function via viral spread block + Fc-dependent mechanisms

2/ From an mpox-convalescent individual, we isolated 3 human monoclonal antibodies (mAbs) (EV35-2, EV35-6, EV35-7) that target the extracellular virion protein A35, essential for viral spread.

🦠 1/ The 2022 mpox outbreak underscored the urgent need for effective therapies. Existing antivirals (e.g., Tecovirimat) showed limited success in trials. We set out to identify new immune-based strategies.

7/ In summary, this platform optimizes “hard” mRNA antigens- those that fail to generate strong responses with conventional designs.

Congrats to first authors Zhenhao Fang & Valter Monteiro, and the entire team. 🎉

5/ Chimeric mRNA vaccines with MVP modules not only induced stronger antibodies but also enhanced T cell responses, improving survival in lethal viral challenge models.

6/ Importantly, the approach is generalizable. Extended to HPV and VZV, showing robust improvements across different viral targets

3/ ⚡MVP allows >2,500 possible combinations of antigen + CST modules, enabling optimization of antigen expression & presentation.

4/ Using mpox virus antigens as models (A29, M1R, A35R, etc.), MVP increased surface expression 100–10,000-fold and boosted antibody responses in mice 🐁.

2/ 💡Modular Vaccine Platform (MVP) helps this by systematically engineering “cell surface translocation” (CST) modules. These are like trafficking signals that ensure antigens are displayed where immune cells can recognize them.

1/ mRNA technology have transformed how we design and deliver vaccines, but not all antigens are equally immunogenic when delivered as mRNA. Some proteins fail to reach the cell surface → weak immune responses.

We urge researchers, editors, and public health professionals to:
– Reassess default epidemiological labels
– Prioritize accuracy over legacy language
– Center transmission routes, not identities

#PublicHealth #Mpox #InfectiousDiseases #StigmaFreeScience

🌎Big thanks to our collaborators at Yale, Brazil, and Portugal!

If you’re interested in vaccines, immunological memory, or emerging viral threats like Mpox, check out the full paper!

Would love to hear your thoughts and questions! 🙌

⚡Our study highlights:

• The importance of antibody effector functions beyond direct neutralization
• The need for booster strategies to broaden and sustain cross-protective immunity
• The role of targeting more conserved viral antigens in future vaccine designs

Remarkably, T cell responses to orthopoxviruses persist up to 80 years after Dryvax vaccination!

But humoral responses to MPXV are weaker and wane faster without boosting.

Boosting doses 💉 increases the magnitude and breath of responses !