Research On Venezuelan Equine Encephalitis Vaccines

Overview

Do you know how to prevent Venezuelan Equine Encephalitis (VEE)? Venezuelan Equine Encephalitis (VEE) is an infectious disease endemic to the Americas.¹ It is a mosquito-transmitted illness that can result in severe neurological complications in affected individuals. The virus predominantly circulates among equines such as horses, mules, and donkeys, occasionally spilling over into human populations.¹ Disease outbreaks generally extend from South America to the southern United States, representing a significant public health challenge.²

Developing effective vaccines against this viral pathogen represents a continuous scientific endeavour to prevent new VEE outbreaks. In this article, we will explore current advances in VEE vaccines. This commences with thoroughly examining the virus, its repercussions, and the persistent efforts to formulate preventative measures using new vaccine technology.

Key takeaways

Understanding venezuelan equine encephalitis

VEE is caused by a mosquito-borne virus primarily affecting equines, occasionally spilling over into human populations. The virus belongs to the Alphavirus genus and is transmitted to humans through the bites of infected mosquitoes, predominantly of the Aedesspecies. Humans can only be infected through a mosquito bite. There is no documented evidence of direct transmission of the virus between humans. 

VEE outbreaks have been registered since the last century. The virus was isolated for the first time in 1938, and documented outbreaks in humans were well-documented for the first time some years later.³ The worst historical outbreak occurred in 1995. Around 75’000 people from Colombia and Venezuela were infected with the VEE virus, from which 3000 developed neurologic complications and 300 died.⁴ This outbreak also caused a huge economic loss due to the infection of 50’000 unvaccinated horses, from which 4000 were lost.⁴

The cyclic nature of these outbreaks is associated with factors such as climate, environmental conditions, and the presence of suitable mosquito vectors. Surveillance and understanding these patterns are vital for anticipating and managing potential outbreaks. Prevention strategies and readiness are necessary since VEE exhibits a persistent epidemiological pattern with noticeable periods of apparent silence in its spread.⁵

The variability in symptomatology adds a layer of complexity to the challenges posed by the disease. The clinical spectrum of VEE in humans ranges from mild flu-like symptoms to severe neurological complications. Among the mildest cases, some symptoms.² include:

• Fever
• Headache
• Body pain
• Nausea
• Vomiting
• Abdominal Pain

The disease resolves in the majority of patients after 2 weeks. However, the most predominant complication is encephalitis, which is the inflammation of the brain and causes other symptoms like headache, fever, fatigue, mental confusion, etc. In the worst-case scenarios, it can lead to the death of infected individuals.⁶

Given the zoonotic nature of VEE, wherein the virus can jump from animals to humans, a holistic approach to disease control involves both veterinary and public health measures. Vaccination plays a pivotal role in preventing VEE in equines, reducing the overall burden of the virus in endemic regions and minimising the risk of human exposure.

The current state of VEE vaccine research

Currently, there are no commercially available vaccines against VEE for humans. Research endeavours have been focused on a better understanding of the virus’ structure⁷ and genes,⁸ as well as exploring the synthesis of new vaccines and their efficacy at a preclinical stage. 

Traditional inactivated vaccines and live attenuated vaccines⁹ have been part of the historical arsenal against VEE. However, the advancement of molecular biology and genetic engineering has accelerated the development of novel vaccine candidates. These platforms allow for precise manipulation of viral components, enhancing vaccine safety and efficacy. Ongoing research is steering towards innovative platforms, including recombinant vector vaccines, viral vectors, subunit vaccines, and messenger RNA (mRNA) vaccines. 

Furthermore, pursuing a safe and effective VEE vaccine involves rigorous pre-clinical studies to assess vaccine candidates' efficacy and safety profiles. The pre-clinical stage involves injecting a vaccine with the virus under an animal’s skin and studying its effects before testing the drug in humans. Once mice are infected with this virus, they go through two phases of the disease. Initially, the virus infects a part of the immune system, and then it progresses to destroy the central nervous system until the mouse dies.¹⁰

Inactivated vaccines

Inactivated vaccines use viruses or bacteria that have been inactivated or killed. These vaccines stimulate an immune response by introducing the inactivated pathogen, preparing the immune system to recognise and combat the infectious form of the microorganism in the future. Scientists created an inactivated vaccine called V4020 by adding modified virus genes that weaken it and protective changes.¹¹ When they tested it on monkeys, the vaccine caused a strong immune response without any harmful side effects, and the monkeys were protected when exposed to the real virus.

Live attenuated vaccines

Attenuated vaccines use live viruses or bacteria that have been weakened or attenuated to the point where they cannot cause disease in healthy individuals. These vaccines prompt a robust immune response, providing long-lasting protection by mimicking a natural infection without causing illness. For example, the TC-83 vaccine was one of the first vaccines against VEE virus. It is made of an attenuated version of the TC-83 strain of VEE virus. When mice were vaccinated with the TC-83 virus, the vaccine worked well when injected under the skin.¹² Additionally, tests in mice using the same inactivated strain revealed that the vaccines remained potent even after prolonged inactivation periods.¹³ V3526 is another attenuated vaccine that has shown its efficacy (and sometimes exhibits higher efficacy than TC-83) in mice,¹⁴ horses,¹⁵ and non-human primates.¹⁶

Recombinant protein vaccines

Recombinant vector vaccines use proteins derived from genetic material, often through genetic engineering or biotechnology. These vaccines use a genetic approach, where a small piece of the virus's genetic material is put inside an inactivated virus. The virus differs from the virus that wants to be controlled and is a carrier for the genetic material. A new vaccine that uses this technology was tested in mice with a part of the HIV virus.  the vaccine showed stronger immune responses even at lower doses than traditional vaccines and didn't cause any immune reaction.¹⁷

Viral particles

Viral particle vaccines use harmless viruses, such as viral proteins or shells, to stimulate an immune response without using the complete virus. The exploration of subunit vaccines aims to induce targeted immune responses while minimising potential side effects associated with whole-virus vaccines. When tested in mice, a novel VEE-based particle showed a strong immune response.¹⁸

mRNA vaccines

One pivotal innovation lies in the advent of mRNA vaccines. These vaccines, exemplified by the success of COVID-19 vaccines, represent a groundbreaking approach that harnesses the virus’s genetic material to stimulate a response from the immune system. By exposing your body to the virus’s genetic material in small amounts, the vaccine teaches your immune system to recognize and fight off the virus without making you sick.

American researchers developed two novel mRNA vaccines that could make vaccine production faster and simpler.  Tests on mice showed that the new vaccines provided strong protection against the VEE virus¹⁹.

The following table²⁰ summarises the advantages and disadvantages of the different vaccines under research against VEE:

Future directions in VEE vaccine research

In the realm of Venezuelan equine encephalitis (VEE) vaccine development, an exciting and promising direction involves exploring next-generation vaccines, integrating cutting-edge technologies like nanotechnology and Artificial Intelligence (AI) applied to vaccine design and development.

Nanotechnology

Nanoparticle-based vaccines utilise extremely small particles, often in the nanometer range, to carry antigens, the components that stimulate the immune system. The controlled and sustained release of antigens from nanoparticles may contribute to prolonged protection, offering a more durable defence against the virus. This technology offers a precise and controlled platform for presenting antigens to the immune system. In the context of VEE, this precise presentation can potentially result in enhanced immune responses.

Artificial intelligence

The integration of artificial intelligence (AI) and computational modeling into vaccine design is another frontier that holds substantial promise. By analysing datasets and predicting potential outcomes, researchers can expedite the identification of optimal vaccine candidates, streamlining the development process and ensuring a more efficient response against VEE.

Implications for public health

Making new VEE vaccines requires global collaborative efforts. Research institutions, pharmaceutical companies, public health organisations, and governments should collaborate to accelerate the production of a new vaccine. These collaborations are essential to facilitating the translation of research findings into accessible vaccines that can be used effectively in endemic regions.

The effectiveness of vaccination extends beyond individual protection. By vaccinating a significant proportion of the population, the transmission of VEE can be substantially reduced, protecting even those who may not be eligible for vaccination due to medical reasons, age, or other factors. This phenomenon is called herd immunity.

It is essential to emphasise the role of education and awareness. Public health campaigns play a pivotal role in disseminating accurate information about VEE, fostering vaccine literacy, and encouraging community-wide participation in vaccination programmes. In this way, we move closer to creating resilient communities that are better equipped to confront VEE on a global scale.

Summary

Research on Venezuelan equine encephalitis (VEE) vaccines aims to develop effective preventive measures against this disease. VEE is a mosquito-borne illness that can affect both horses and humans. Scientists are working on vaccines to protect individuals from the virus.

The goal of a vaccine is to stimulate the immune system to recognise and fight the VEE virus, preventing infection or reducing the severity of symptoms if a person is exposed. This research involves studying different vaccine formulations and strategies, assessing their efficacy through preclinical studies, and determining their long-term effectiveness. New technologies like nanotechnology and AI can be used to develop new vaccines against VEE. 

While the research involves complex scientific processes, the final target is to develop a vaccine that is not only trustworthy but also accessible and understandable to the general public. Monitoring updates in VEE vaccine research can contribute to informed decisions about personal and public health.