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Hope on the Horizon: New Vaccine for Powassan Virus

A promising vaccine approach could combat the Powassan virus effectively.

Michael W. Crawford, Walid M. Abdelwahab, Karthik Siram, Christopher J. Parkins, Henry F. Harrison, Samantha R. Osman, Dillon Schweitzer, Jay T. Evans, David J. Burkhart, Amelia K. Pinto, James D. Brien, Jessica L. Smith, Alec J. Hirsch

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Table of Contents

Powassan virus (POWV) is a type of virus that spreads through tick bites. It is mostly found in North America and parts of Far Eastern Russia. This virus can make people very sick, leading to serious brain problems and even death in some cases. The scary part is that around 12% of people who get sick from POWV may die from it. Among those who survive, about half might have lasting problems with their nerves or brain functions.

While POWV infections used to be quite rare, it seems that more and more people are getting infected, especially in the northeastern United States and the Great Lakes regions. This area is home to ticks that carry the virus, particularly the Ixodes cookei and Ixodes scapularis ticks. With climate change making things warmer, there is a chance that these ticks-and the virus they carry-might spread to new areas.

Currently, there is no vaccine or treatment for POWV. This lack of medical options is a growing concern for public health, making the need to prioritize the development of a vaccine even more urgent.

What is a Virus-like Particle (VLP) Vaccine?

VLP vaccines are a potential solution for creating a vaccine against POWV. These vaccines are made of virus proteins that come together to form a structure resembling the actual virus. However, they do not contain any actual virus, which makes them safer. This is a big advantage over traditional vaccines that might use weakened or killed viruses.

Specifically, the VLPS related to POWV can be made by using certain proteins from the virus, which can help the immune system recognize and fight the virus without the risks associated with live viruses. Studies have shown that these VLP vaccines can not only stimulate strong antibody responses but can also help the immune system fight the virus in other ways.

The Role of Adjuvants in Vaccines

Adjuvants are substances added to vaccines to improve their effectiveness. They help to kickstart the immune response and ensure that the body remembers the virus if it encounters it again in the future. One of the popular adjuvants is alum, which has been traditionally used in vaccines for many years.

However, there are many other adjuvants that have shown promise in research. One such promising agent is a TLR7/8 agonist called INI-4001, which has shown potential to improve how well vaccines work, especially in eliciting strong Immune Responses.

Testing a New Vaccine for Powassan Virus

Recent studies have tested a new POWV vaccine that uses the VLP technology, combined with different adjuvants to see which one works best. In animal trials, the VLP vaccine was combined with either alum, INI-2002, or INI-4001. The goal was to compare how well these different combinations produced immune responses.

The findings showed that the combination with INI-4001 significantly boosted the body's ability to produce neutralizing Antibodies against the virus compared to other combinations. This means that not only did the vaccine help protect the animals from illness, but it also appeared to last longer.

The Effectiveness of INI-4001

Animals vaccinated with the VLP vaccine combined with INI-4001 showed amazing results. They had a much stronger immune response, which included producing antibodies that could neutralize the virus more effectively. Even when these animals were exposed to the virus later on, they fared much better than those vaccinated with other combinations.

For instance, when faced with a lethal dose of the virus, all the vaccinated animals using INI-4001 survived, while those with other adjuvants didn’t do nearly as well. This shows the potential of INI-4001 to enhance the effectiveness of the vaccine against POWV.

The Importance of Reducing Viral Load

One of the main concerns with POWV is its ability to invade the brain and cause serious problems. Therefore, it was important for the research to look at how well the different vaccine combinations reduced the amount of virus present in key organs such as the brain, liver, and spleen after infection.

Animals that were given the vaccine with INI-4001 not only had lower amounts of the virus in their brains, but they also showed fewer signs of illness. This added evidence that the vaccine could effectively protect against not just infection, but also the harmful effects that come from a viral invasion of the brain.

Passive Transfer of Antibodies

In another interesting experiment, researchers wanted to see if they could protect naïve mice (mice that had not been vaccinated) by transferring antibodies from vaccinated mice. This approach is like giving someone a ready-made shield against the virus.

It turned out that when these naïve mice received the antibodies from the mice vaccinated with the INI-4001 vaccine, many of them survived the virus challenge, demonstrating that the antibodies were indeed helping to protect them. This reinforces the role of antibodies in providing immunity against the POWV.

Is T Cell Response Necessary?

While antibodies are important, researchers were curious whether T cells, another part of the immune system, played a role in protection. They tried depleting T cells from vaccinated mice prior to exposing them to the virus.

Interestingly, even after depleting these T cells, the vaccinated mice still managed to survive the virus challenge. This result suggests that the protection offered by the vaccine was primarily due to the antibodies it produced, at least in the early stages of the immune response.

Cross-Reactivity with Other Viruses

Another significant part of the research aimed to see if the vaccine could provide immunity not just against POWV-I but also against other similar viruses, particularly POWV-II. The results were promising, as the mice vaccinated with INI-4001 produced antibodies that recognized both POWV-I and POWV-II, as well as a related virus known as Langat virus.

This broad antibody response is important because it increases the likelihood of the vaccine being effective against multiple strains and related viruses. In fact, when challenged with POWV-II, the vaccinated animals showed great protection compared to those that received the standard alum adjuvant.

Long-lasting Protection

The durability of the immune response is a crucial aspect of any vaccine. Researchers measured the levels of antibodies produced over many months following vaccination. The results were clear: the INI-4001 adjuvanted vaccine not only produced a stronger initial response but also maintained higher antibody levels for a longer period compared to the alum.

Even after several months, a significant number of animals vaccinated with INI-4001 were still able to neutralize the virus, indicating that this vaccine could provide long-lasting protection.

Conclusion: A Bright Future for Powassan Virus Vaccination

The emergence of POWV as a public health risk means that finding an effective vaccine is of paramount importance. The combination of VLP technology with promising new adjuvants like INI-4001 represents a step forward in creating a vaccine that may help fight against this dangerous virus.

Through rigorous testing, researchers have shown that this new approach can significantly improve the immune response, provide protection against multiple strains, and last longer than traditional formulations. As the fight against tick-borne diseases continues, the development of such vaccines may well become a vital tool in public health strategies.

So, as we look ahead, it seems that with the right tools and research, we might just win the battle against those pesky ticks and the viruses they carry. And while we may not have a tick-repelling superhero quite yet, we are definitely on the right path to keeping people safe and healthy.

Original Source

Title: The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine

Abstract: Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develop a POW virus-like-particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001. We demonstrate that INI-4001 outperforms both alum and the Toll-like receptor 4 agonist INI-2002 in enhancing the immunogenicity of a dose-sparing POW-VLP vaccine in mice. INI-4001 increases the magnitude and breadth of the antibody response as measured by whole-virus ELISA, induces neutralizing antibodies measured by FRNT, reduces viral burden in the brain of infected mice measured by RT qPCR, and confers 100% protection from lethal challenge with both lineages of POWV. We show that the antibody response induced by INI-4001 is more durable than standard alum, and 80% of mice remain protected from lethal challenge 9-months post-vaccination. Lastly, we show that the protection elicited by INI-4001 adjuvanted POW-VLP vaccine is unaffected by either CD4+ or CD8+ T cell depletion and can be passively transferred to unvaccinated mice indicating that protection is mediated through humoral immunity. This study highlights the utility of novel synthetic adjuvants in VLP-based vaccines. Author summaryPowassan virus (POWV) is an emerging pathogenic tick-borne flavivirus for which there is no vaccine. Current tick-borne flavivirus vaccines are less than ideal and use formalin-inactivated virus adjuvanted with alum. These vaccines require thorough inactivation of the antigen and frequent boosting to maintain immunity. In this study, we describe the development of a POWV vaccine using Powassan virus-like-particles (POW-VLPs) adjuvanted with either of two novel Toll-like receptor (TLR) agonists, the TLR4 agonist INI-2002 or the TLR7/8 agonist INI-4001. We show that INI-4001 enhances the antibody response, reduces POWV neuroinvasion, and elicits full protection from lethal POWV infection in mice prime-boost vaccinated with low doses of POW-VLP. We further show that this protection is mediated by a humoral immune response which is both broader and more durable than a POW-VLP vaccine formulated with alum. These findings demonstrate the effectiveness of the novel synthetic TLR7/8 agonist INI-4001 as an adjuvant for low-dose VLP-based vaccines and the ability of this vaccine platform to improve upon current tick-borne flavivirus vaccine methodology.

Authors: Michael W. Crawford, Walid M. Abdelwahab, Karthik Siram, Christopher J. Parkins, Henry F. Harrison, Samantha R. Osman, Dillon Schweitzer, Jay T. Evans, David J. Burkhart, Amelia K. Pinto, James D. Brien, Jessica L. Smith, Alec J. Hirsch

Last Update: 2024-12-03 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.11.28.625832

Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.28.625832.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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