Blog

July 2025

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When three monkeys (a howler, a white-faced monkey, and a spider monkey) were found dead in a forested area of Colombia’s Putumayo department, what might have previously gone unnoticed became an early warning sign that triggered a swift, coordinated response to contain a yellow fever outbreak. This time, the difference was knowledge.

“Thanks to the training we received on proper sample collection in primates, we were able to detect a yellow fever outbreak after discovering three dead monkeys at the same time,” said Wilder Pérez, from the Putumayo Health Secretariat’s Vector-Borne and Zoonotic Disease Program. “Without that knowledge, the animals might have been buried without analysis — and we would have missed a critical opportunity to act.”

Wilder had participated months earlier in a regional workshop on epizootic and vector surveillance, organized with technical support from the Pan American Health Organization (PAHO). During the training, health teams were instructed on the safe collection of samples from wildlife, vector surveillance, and intersectoral coordination.

The workshop, held in Tolima—another key department in Colombia’s current yellow fever response—proved crucial for enabling the Putumayo team to act swiftly when the first signs of the virus emerged.

The training paid off. Once the dead monkeys were reported, immediate measures were taken — vaccinating environmental workers, conducting entomological studies, and analyzing the affected area. As a result, the surveillance system not only confirmed the presence of the virus, but also prevented its spread to nearby urban areas.

Tolima, in turn, is facing the most severe yellow fever outbreak recorded in the country outside the Amazon region. Since late 2024, the department has confirmed 95 human cases of yellow fever and 35 deaths. Most cases occurred in rural areas near the Galilea Forest Regional Natural Park — a dense, biodiverse jungle where humans, monkeys, and mosquito vectors coexist.

Influenza hemagglutinin subunit vaccines are more effective and offer better cross protection against various influenza virus challenges when combined with a mucosal adjuvant that enhances the body’s immune response, according to a study by researchers in the Institute for Biomedical Sciences at Georgia State University.

The study published in the journal ACS Nano shows that immune cell-derived extracellular vesicles, specifically those from mature bone marrow-derived dendritic cells (which are crucial for immune responses), rather than those from immature dendritic cells, are potent mucosal adjuvants for influenza hemagglutinin vaccines.

The influenza hemagglutinin subunit vaccine is a type of influenza vaccine that primarily contains the surface protein hemagglutinin of the influenza virus. Mucosal adjuvants are substances that can enhance the body’s immune response to foreign materials in the mucosa, such as the surface of the respiratory tract, study authors explained.

Existing seasonal influenza vaccines have limited effectiveness against evolved virus strains, so next-generation, cross-protective influenza vaccines are urgently needed. Recombinant protein subunit vaccines have gained attention in vaccine development due to their safety, ease of large-scale manufacturing and affordability. Protein subunit vaccines can be designed to target specific pathogen components, leading to more focused immune responses.

Studies have found that mucosal immunization is a promising strategy against respiratory infectious diseases because it helps prevent the infection and transmission of respiratory pathogens and exhibits potential cross protection. However, the effectiveness of protein vaccines administered mucosally is limited, so there’s a need for safe and effective mucosal adjuvants. This study investigated the potential of extracellular vesicles derived from mature dendritic cells as mucosal adjuvants for influenza hemagglutinin vaccines.

Prior to this study, the mucosal adjuvant potential of extracellular vesicles derived from mature dendritic cells and the underlying mechanisms of action have been unknown.

Immune cell-derived extracellular vesicles, which play crucial roles in intercellular communication and modulating biological responses, are potent mucosal adjuvants for influenza hemagglutinin vaccines.” 

Bao-Zhong Wang, senior author of the study and a Distinguished University Professor in the Institute for Biomedical Sciences at Georgia State

“These vesicles exhibit intriguing immunostimulatory activity both in vitro and in vivo,” Wang said. “Specifically, they effectively activated antigen-presenting cells, macrophages and B cells in vitro, and promoted enhanced recruitment of airway immune cells, early lymphocyte activation and robust germinal center formation in mice.”

The study found that intranasal immunization of mice with the influenza hemagglutinin vaccine plus the extracellular vesicle adjuvant from mature bone marrow-derived dendritic cells elicited significant, cross-reactive, and multifaceted humoral and cellular immune responses at both systemic and mucosal sites, conferring complete protection against homologous and heterologous influenza virus challenges.

The researchers pointed out that extracellular vesicles derived from mature dendritic cells have gained significant attention in immunotherapy and vaccine development because they have a variety of immunologically active molecules crucial for effective presentation of antigens (foreign substances that induces an immune response in the body), as well as cell adhesion and fusion.

“These findings underscore the potential of extracellular vesicles from mature bone marrow-derived dendritic cells as a promising adjuvant or immunomodulatory target for the development of mucosal vaccines,” said Chunhong Dong, first author of the study and a postdoctoral fellow in the Institute for Biomedical Sciences at Georgia State. “Given their biocompatibility and solid adjuvanticity, mature bone marrow-derived dendritic cells represent a promising adjuvant candidate for mucosal vaccine development.”

Additional authors of the study include Lai Wei, Wandi Zhu, Joo Kyung Kim, Ye Wang, Priscilla Omotara and Arini Arsana of the Institute for Biomedical Sciences at Georgia State.

The study is funded by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID).