In the fight against a devastating disease that affects both dogs and humans, scientists are harnessing the power of the immune system to create a new generation of protective vaccines.
Imagine a threat so small it's invisible to the naked eye, yet so formidable it claims tens of thousands of human and canine lives each year. This silent enemy is Leishmania infantum, a parasitic organism that causes visceral leishmaniasis, the most severe form of a disease known as leishmaniasis.
While in humans the disease can be fatal if untreated, dogs bear the heaviest burden as the main reservoir of the parasite in urban areas.
Human cases annually worldwide
Dogs at risk in endemic areas
Protection rate of LmCen⁻/⁻ vaccine
Recent breakthroughs in vaccine technology are now offering hope in this long-standing battle. A comprehensive analysis of current research reveals that certain types of vaccines are proving significantly more effective than others in protecting our canine companions 1 . The development of these vaccines represents not just a victory for veterinary medicine but a crucial step forward in public health, creating what scientists call a "canine shield" that protects both dogs and humans from this devastating illness.
To appreciate the challenge of creating an effective vaccine, we must first understand the complex life cycle of this clever parasite. Leishmania infantum is transmitted through the bite of infected sand flies—tiny insects known by various local names like "straw mosquito" or "birigui" 2 .
When an infected sand fly bites a dog or human, it injects the parasite in its promastigote form into the skin.
Once inside the host, these parasites are engulfed by macrophages—the very immune cells that normally destroy invaders. In a remarkable evolutionary adaptation, Leishmania parasites have developed the ability to survive and multiply within these immune cells by using a special surface coating of lipophosphoglycan (LPG) molecules that prevents the macrophage from destroying them .
Infected sand fly injects promastigotes into the host's skin
Promastigotes are phagocytized by macrophages
Promastigotes transform into amastigotes inside macrophages
Amastigotes multiply and infect new cells, spreading to organs
The key to an effective vaccine lies in understanding the complex immune response to Leishmania infection. Research has revealed that the outcome of infection depends heavily on the type of immune response the host mounts 9 .
A successful immune response—one that controls the parasite without causing excessive tissue damage—relies on what immunologists call a Th1-type response. This response is characterized by the production of specific chemical messengers including:
These cytokines activate infected macrophages to produce nitric oxide and reactive oxygen species that ultimately kill the intracellular parasites 9 .
Controls parasite through IFN-γ, IL-12, TNF-α
Worsens disease through IL-4, IL-10
In contrast, a Th2-type response, associated with different cytokines like IL-4 and IL-10, tends to worsen the disease by suppressing the Th1 response and allowing the parasite to multiply unchecked . The balance between these two responses often determines whether an infected dog remains healthy or develops clinical disease.
This immunological understanding provides the blueprint for an effective vaccine: it must stimulate a strong, sustained Th1 response while minimizing the Th2 response.
Scientists have approached the challenge of vaccinating against canine visceral leishmaniasis (CVL) from multiple angles. A recent systematic review and meta-analysis published in 2025 examined 22 studies to compare the efficacy of different vaccine types 1 . The research revealed clear differences in performance among three main approaches:
| Vaccine Type | Mechanism of Action | Efficacy Against Parasites in Organs | Efficacy Against Clinical Signs |
|---|---|---|---|
| DNA Vaccines | Introduce parasitic DNA to trigger immune recognition | Not statistically significant | Not statistically significant |
| Subunit Vaccines | Use specific parasitic proteins to stimulate immunity | Statistically significant | Not statistically significant |
| Excreted/Secreted Protein Vaccines | Utilize proteins released by live parasites | Significantly more effective than DNA vaccines | No significant difference |
This hierarchy of effectiveness makes biological sense. Subunit and excreted/secreted vaccines present the immune system with proteins that the parasite naturally exposes to the host during infection, giving the immune system a more accurate preview of what to recognize and attack during a real infection.
Among the most promising recent developments is a vaccine based on a genetically modified version of the parasite itself. Scientists created what's known as a live attenuated vaccine by using CRISPR-Cas9 gene editing technology to delete the Centrin gene from Leishmania major parasites 7 .
The Centrin gene produces a protein that is essential for the parasite's ability to divide and multiply, particularly inside host cells 7 . Without this gene, the parasites can still briefly infect hosts and stimulate an immune response, but they cannot cause full-blown disease—making them ideal vaccine candidates.
Centrin gene identified as essential for parasite division
CRISPR-Cas9 used to precisely delete Centrin gene
Resulting LmCen⁻/⁻ parasites cannot cause disease
Attenuated parasites used as live vaccine
To test the effectiveness of this LmCen⁻/⁻ vaccine, researchers designed a rigorous field trial that closely mimicked natural conditions 7 . The study involved:
LmCen⁻/⁻ parasites grown under GLP standards
Initial testing on 12 beagle dogs for safety and immunogenicity
Second injection administered two months after initial dose
Dogs transferred to endemic area in Tunisia for natural challenge
The findings from this field trial were impressive 7 :
| Group | Number of Dogs | PCR Positive for Leishmania | Clinical Signs of Disease | Protection Rate |
|---|---|---|---|---|
| Vaccinated | 11 | 1 | 1 | 82.5% |
| Unvaccinated | 11 | 4 | 4 | - |
The vaccinated dogs showed strong antigen-specific cellular responses with IFN-γ production by CD4+ T cells within one month after immunization—exactly the type of Th1 immune response associated with protection against leishmaniasis 7 .
Furthermore, the vaccine demonstrated an excellent safety profile with no serious adverse reactions observed. Hematological and biochemical parameters remained largely within normal ranges after immunization, indicating the vaccine was well-tolerated 7 .
This study was particularly significant because it tested the vaccine under natural transmission conditions, where dogs were exposed to infected sand fly bites—the same way dogs normally acquire the infection in endemic areas.
Developing effective vaccines against complex parasites like Leishmania requires a diverse array of specialized tools and reagents. Here are some of the essential components in the researcher's toolkit:
| Tool/Reagent | Function in Vaccine Development | Application Example |
|---|---|---|
| Recombinant Proteins | Specific parasitic antigens that stimulate targeted immune responses | A2 protein in Leish-Tec® vaccine 2 |
| Saponin Adjuvants | Enhance and modulate the immune response to vaccine antigens | QA-21 in CaniLeish® vaccine 6 |
| CRISPR-Cas9 Gene Editing | Create live attenuated parasites by deleting essential genes | Centrin gene deletion in LmCen⁻/⁻ vaccine 7 |
| Flow Cytometry | Analyze immune cell populations and their cytokine production | Measuring CD4+ and CD8+ T cell responses 7 |
| SYRCLE's RoB Tool | Assess risk of bias in animal studies for systematic reviews | Evaluating quality of vaccine studies 1 |
Whole killed parasites
Recombinant proteins
DNA and live attenuated vaccines
Pros: Strong, comprehensive immune responses
Cons: Potential safety concerns despite testing
Pros: Excellent safety profiles
Cons: May require stronger adjuvants for potent immunity
The world of canine leishmaniasis vaccines has seen significant changes recently. As of 2025, two commercially available vaccines are being used to prevent the disease: Neoleish® and LetiFend® 2 . Meanwhile, Leish-Tec®, previously licensed for use in Brazil, was suspended in May 2023 due to non-compliance in some batches, similar to CaniLeish®, which was discontinued by the European Commission in October 2023 2 .
Combining several Leishmania proteins to enhance protection across different parasite strains 3
Developing adjuvants that effectively steer the immune system toward a protective Th1 response without excessive inflammation 2
Creating challenge models that better replicate natural transmission conditions 7
The progress in developing effective vaccines against canine visceral leishmaniasis represents a triumph of the "One Health" approach—the recognition that human, animal, and environmental health are inextricably linked 3 . As Dr. Clarisa B. Palatnik-de-Sousa and her colleagues noted, "ZVL is a disease that epitomizes perfectly the need for a One Health approach since the disease occurs in both dogs and humans" 3 .
The development of increasingly effective vaccines not only protects our canine companions from a devastating disease but also reduces the transmission of parasites to humans, potentially lowering the incidence of human visceral leishmaniasis. As research continues to refine these biological shields, we move closer to a future where both dogs and humans in endemic areas are protected from this ancient scourge.
With continued research and development, scientists are building better canine shields—strengthening the barrier between this deadly parasite and the families, both human and canine, that it threatens.