Recently accredited as a supervisor in the Graduate Program in Pharmacology at UNICAMP, Prof. Dr. Luís Gustavo Romani Fernandes investigates ways to improve immunotherapy for the treatment of wasp venom allergy in Brazil.
In this article, we take a closer look at his current research, presenting its challenges and its relevance to society. The article is also an invitation for those interested in joining Prof. Luís’s research group, as he is currently seeking new master’s and doctoral students, as well as technical training fellows.
Prof. Luís holds a degree in Biological Sciences and a PhD in Genetics and Molecular Biology, with a specialization in Immunology, from UNICAMP. He also completed postdoctoral training at UNICAMP in the Laboratory of Translational Immunology (LIT) at the School of Medical Sciences (FCM), coordinated by Prof. Dr. Ricardo de Lima Zollner, and more recently at the Laboratory of Dermatology and Experimental Allergy at Justus Liebig University (Giessen, Germany). He is currently a researcher and biologist at the LIT. Since his doctoral studies, he has been investigating the regulation of the immune response.
Today, Prof. Luís’s main line of investigation focuses on evaluating the cellular and molecular mechanisms involved in the regulation and activation of innate and adaptive immunity directed at allergens present in the venoms of Hymenoptera (bees, wasps, and ants). Within this line of research, he holds a research grant from FAPESP (process no. 24/23516-7) entitled: “Evaluation of the potential use of hypoallergenic variants derived from the Poly p 1 and Poly p 5 allergens from the venom of the wasp Polybia paulista in allergen-specific immunotherapy protocols.”
When a sting can become fatal
Anyone who has watched the 1991 film My Girl may still carry emotional memories of one of the most unexpected deaths in cinema. If you haven’t seen it yet, I’m sorry for the spoiler. In the movie, we follow the friendship between Vada (played by Anna Chlumsky) and Thomas (Macaulay Culkin). The children’s touching story comes to an abrupt end when Thomas is attacked by a swarm of bees. Because he is extremely allergic, he suffers an anaphylactic reaction that leads to his death.
As illustrated in the film, Hymenoptera stings can be potentially fatal due to the risk of anaphylaxis. Anaphylaxis is an exaggerated allergic reaction that some patients may experience. It may involve a sudden drop in blood pressure, shortness of breath due to airway constriction, swelling, redness and itching of the skin (urticaria), and the risk of death within minutes.
The film portrays a real clinical problem investigated by the research group in studies initiated by Prof. Zollner in patients who presented this type of response. The group focused on exploring both the venom components that trigger these reactions, known as allergens, and the immune response mechanisms involved in this process.
The limits of current therapies for venom allergies
Currently, the treatment of anaphylaxis has some limitations. Prof. Luís explains: “When a patient experiences this condition, they are treated with drugs that mainly act on the symptoms: they stabilize the patient and block the anaphylactic reaction, but they do not modify the response over time. There is a way to modify this response, which we call immunotherapy.” Immunotherapy uses the venom itself to treat the allergic response to the venom. Over time, it can shift the immune response toward a non-harmful profile. Thus, if the individual is stung again, they may still experience reactions, but the condition will be milder, reducing the risk of death.
Immunotherapy is already used in some parts of the world, but it still needs improvement. Adverse effects may occur as a result of venom administration, such as exaggerated reactions during treatment in some patients and the induction of harmful responses to other venom components to which the patient had not previously reacted, a phenomenon known as sensitization to new allergens.
For this reason, in his FAPESP-funded project, Prof. Luís seeks to improve immunotherapy through an approach aimed at reducing these adverse effects. He explains: “The idea is to generate the main components of the venom that modulate the response: the allergens. We want to produce modified allergens capable of modulating the immune response without triggering unwanted reactions. This strategy is called the use of hypoallergenic variants.”
Rewriting the “recipe” of venom
Researchers can now produce venom allergens in the laboratory without needing the wasp itself. Prof. Luís explains how the process works: “We extract RNA from the venom glands of wasps, locate the allergen gene, and clone this gene into expression vectors.”
This process is similar to obtaining a copy of the “recipe book” that wasps use to produce the components of their venom: the cDNA obtained from the messenger RNA of the venom glands. Researchers then identify only the pages containing the “recipes” of interest: the specific allergen genes. Finally, these recipes are given to other “cooks” to produce the allergens: the expression vectors. These vectors may be bacteria (such as Escherichia coli), yeast cells, or even cells from other insects.
Once the gene has been cloned, researchers can introduce mutations through genetic engineering to obtain hypoallergenic variants. The key step is identifying the region of the allergen molecule known as the epitope. This is the region where a type of antibody produced by the patient, called immunoglobulin E (IgE), binds. This binding is the first step in triggering the anaphylactic response. Therefore, locating the epitopes is essential. If the allergen molecule is modified so that this epitope is no longer present, IgE binding will not occur and, consequently, the anaphylactic reaction will not be triggered. This is how hypoallergenic variants are created: allergen molecules modified to avoid triggering an unwanted immune response.
Returning to the recipe-book metaphor, introducing these mutations is similar to modifying a recipe. Researchers must identify the part of the gene responsible for producing the epitope, just as one would identify the part of a recipe that instructs adding a specific ingredient. If that ingredient is undesirable, the recipe can be altered by removing it or replacing it with another. This modification corresponds to a genetic mutation. In this way, a recipe (gene) that once instructed the preparation of a cornmeal cake with anise seeds (the original allergen) could be modified to remove the anise (the epitope), resulting in a plain cornmeal cake (the hypoallergenic variant).
Why studying Brazilian wasps is important
One major interest of the study is the possibility of creating immunotherapeutic products with potential future clinical applications in immunotherapy protocols. Currently, treatment relies on imported immunotherapeutic products, which significantly increases costs.
Another important aspect is the use of wasp species prevalent in Brazil. At present, immunotherapy is performed using venom from wasps common in other countries, such as the yellow jacket wasp from the United States. In his project, however, Prof. Luís uses allergens derived from the venom of the wasp Polybia paulista (locally known as “marimbondo-paulistinha”), a species known for the frequency of accidents, especially due to its aggressiveness and adaptation to urban environments. It can be found in the Brazilian states of São Paulo, Minas Gerais, Goiás, Mato Grosso, and Paraná, as well as in other Latin American countries such as Argentina.
The allergens selected to generate the hypoallergenic variants are Poly p 1 and Poly p 5 from Polybia paulista venom. Prof. Luís’s research group, in collaboration with Prof. Dr. Mario Sergio Palma and the now-retired Prof. Dr. Márcia Regina Brochetto Braga, both from the Institute of Biosciences in Rio Claro (UNESP), performed immunological and biochemical characterization of these allergens in their natural and recombinant forms expressed in yeast. These are the allergens that most frequently cause anaphylactic reactions in the venom.
Another factor that may aggravate cases of anaphylaxis is climate change. Prof. Luís warns that cases of wasp stings are increasingly being reported in new regions: “Cases of anaphylaxis have already been described in Alaska. […] Changes caused by global warming are leading colder countries to begin reporting accidents involving species that were previously not found there.” As a result, more stings from species such as Polybia paulista and, consequently, more cases of anaphylaxis may occur in the future.
From the laboratory to potential clinical application
If the use of hypoallergenic variants in the immunotherapy prove to be safe, thefuture is promising. Prof. Luís explains: “We aim to transform this biotechnological product into a new pharmaceutical formulation. There is great potential for patent generation. Contacts with Inova (UNICAMP’s Innovation Agency) are already underway.” However, he emphasizes that many studies are still required before a patent can be filed. At the moment,in vitro studies (without the use of animals) and experiments in laboratory animals (mice) are being conducted. Only then will the project be able to move forward to clinical trials in humans.
Prof. Luís also highlights the importance of using experimental animals: “I would love to have an artificial or in vitro system capable of mimicking the full complexity of the anaphylactic response. Unfortunately, we still do not have models that can fully replace the use of animals.” The group uses well-established models of anaphylactic response with BALB/c mice, which, when exposed to venom, produce a Th2-type response similar to that observed in allergic individuals.
At present, another major focus of the research is ensuring the safety of the hypoallergenic variants in immunotherapy. Prof. Luís notes: “Another important point our project aims to evaluate is the toxicity of these compounds. […] One of the toxic effects of Hymenoptera venoms is kidney injury.” The laboratory is located at the Integrated Center for Nephrology. In collaboration with Prof. Dr. Marilda Mazzali, coordinator of the Laboratory for Transplantation Research, and Prof. Dr. Marcos Vinicius de Sousa, both nephrologists, the group will evaluate renal toxicity in an experimental mouse model. Only after the variants are proven safe in animal models will studies advance to humans.
The project is currently in the epitope localization stage. Preliminary results on the in vitro production of allergens were presented in October 2025 at the XLIX Congress of the Brazilian Society of Immunology (Búzios, Rio de Janeiro) by Laís Stephanie Minati (master’s student) and Juliana de Assis Chagas (undergraduate research student). Other students funded by FAPESP directly involved in the project include Beatriz Pinheiro Furlanetto (undergraduate research fellowship, process no. 25/14584-1) and Milena Fajani Franchikoski (technical training fellowship, process no. 25/20426-0).
The group is opening positions for new researchers
Prof. Luís is currently looking for new researchers interested in joining his group. The FAPESP research grant includes TT-1 and TT-3 fellowships (Technical Training levels 1 and 3). For these opportunities, the professor is seeking individuals who are currently pursuing (TT-1) or have already completed (TT-3) undergraduate degrees in biological sciences. He is also looking for prospective master’s and doctoral students.
Requirements include basic undergraduate-level knowledge of Immunology and Molecular Biology; proficiency in basic laboratory techniques (pipetting, principles of immunoassays and molecular analyses, etc.); and a willingness to learn. Candidates are expected to have a curious and proactive profile when searching for new articles, techniques, and experimental approaches. Interested individuals should contact luisgrf@unicamp.br by email.
By investing in hypoallergenic variants, Prof. Luís’s research aims to improve the immunotherapy, making it safer and more accessible. Furthermore, the project contributes to building a strategic path for Brazilian science: developing technologies and solutions adapted to our epidemiological reality while strengthening national scientific and pharmaceutical autonomy. Initiatives like this demonstrate how basic and translational research can lead to concrete innovation with real potential to save lives.
To learn more:
Polybia paulista (DOI: 10.5212/PUBL.BIOLOGICAS.V.26.I1.0001)
Poly p 1 (DOI: 10.1016/j.toxicon.2016.11.006)
Poly p 5 (paper 1) (DOI: 10.3390/toxins13120850)
Poly p 5 (paper 2) (DOI: 10.3390/toxins9090259)
Written by:
Mia Schezaro Ramos
Pharmacist. Ph.D. in Pharmacology. Science journalist, illustrator, trans, Nintendo enthusiast, K-pop fan, and dependent on physical exercise to stay sane.