The immune response against the AlloPrime vaccine can influence the response to a virus (like the coronavirus that causes COVID-19).
What if you could get one vaccine that protects you against a wide spectrum of viruses, even viruses we havent discovered yet? That might sound impossible and futuristic, but this is just what Immunovative Therapies and its sister company Mirror Biologics, Inc. are aiming to achieve. Their new pan-viral vaccine called AlloPrime is slated to begin a Phase I/II trial next month.
Our pan-viral vaccine harnesses the same protection mechanism that naturally protects us from viral diseases a healthy immune system, Michael Har-Noy, MD, Ph.D., Founder and CEO of Immunovative Therapies, told BioSpace. By remodeling the elderly immune system with a vaccine, we can arm the system to rapidly respond to a viral encounter in the same manner that a young immune system responds to a novel viral encounter.
Just as our body slows down with age, so does our immune system. AlloPrime focuses on remodeling the weakened older immune system by a mechanism known as heterologous immunity. Heterologous immunity occurs when the immune response to one pathogen causes an enhanced response to a later unrelated pathogen. This means that the immune response against the AlloPrime vaccine can influence the response to a virus (like the coronavirus that causes COVID-19).
Im sure the timeliness of strengthening the elderly immune system isnt lost on you COVID-19 heavily impacts older adults. In fact, 80 percent of COVID-19 deaths in the United States have been in people 65 years and older.
As the majority of younger individuals exposed to the virus that causes COVID-19 are either asymptomatic or have mild symptoms, protecting the vulnerable elderly population would enable opening of the economy and building of herd immunity without an increase in hospitalizations and deaths, commented Dr. Har-Noy.
Older adults usually have a weaker response to vaccines, so even if an effective COVID-19 vaccine is created, it could be less protective in older adults, the population that needs protection the most. Thats what is unique about this pan-viral vaccine it focuses specifically on modulating the elderly immune system. AlloPrime could be given as an immune modulator to the elderly on its own or it could be administered as an adjuvant with other vaccines to boost their effectiveness.
In respiratory viral infections that can be transmitted person-to-person, it is especially important to protect the vulnerable elderly population, Dr. Har-Noy said. There is no guarantee that current vaccine technologies, which focus on eliciting neutralizing antibodies, will work to develop a COVID-19 vaccine that is why having a plan B that focuses on a cellular anti-viral immune response is so important, specifically one that targets the most vulnerable.
Immune system basics
Before we get into the nitty gritty details, lets go over the basics of the immune system. Your immune system is the collection of specialized cells and molecules that fight invading pathogens, like viruses and bacteria.
There are two main branches: innate immunity is the quick, non-specific first line of defense, and adaptive immunity is the slower, pathogen-specific response. There are also two types of adaptive immunity: responses that involve cells that destroy pathogens or infected cells (cell-mediated immunity), and responses that involve making antibodies to tag the pathogen for destruction (humoral immunity).
If the pathogen hides inside cells, like viruses do, then creating antibodies against the virus may not provide the most comprehensive protection as they tend to recognize things outside the cell. Generating a cell-based immune response against a virus could provide more robust, longer-lasting protection.
Knowing the optimal immune response to a virus is especially important now. Understanding how COVID-19 affects cell-mediated and antibody-based immunity will be crucial to determining immunity and developing an effective COVID-19 vaccine.
How is this pan-viral vaccine different than other vaccines?
Current vaccine development usually focuses on stimulating the production of antibodies against the virus of interest. This relies not only on knowing what virus you are targeting, but also on having a deep understanding of the virus molecular structure. Most vaccines directly use viral information (such as viral genetic material, viral pieces, or even whole, weakened virus) to attempt to train the persons immune system to recognize and destroy the virus.
Although this method has generated the multitude of efficient vaccines currently available, it has come up short for creating vaccines against certain viruses, such as HIV, Zika, and other pandemic coronavirus strains (such as those that caused SARS and MERS).
Even if a vaccine can successfully generate antibodies against a virus, the vaccine may be rendered less effective or useless if the virus mutates; the antibodies wouldnt recognize the viral mutant as well (if at all). This happens with the various strains and mutations of the flu virus, which is why you need to get an annual flu shot to stay protected.
Immunovatives vaccine, however, isnt reliant on the virus it focuses on the cell-mediated immune response rather than virus-specific antibodies. The vaccine supplements a persons immune system by providing living bioengineered foreign immune cells, called AlloStim, that arent virus-specific. Instead, these foreign cells elicit a powerful immune response that creates a swarm of immune cells ready to sound the alarm and fight future viral invaders.
Rather than trying to figure out which viral peptides are immunogenic or could display on MHC molecules, our approach focuses on the natural immune response, which starts with the cellular innate immune response, Dr. Har-Noy said. Our vaccine would provide pan-viral protection to the most vulnerable population without needing to know the viral structure, including protection against COVID-19 viral mutants and the next viral pandemic that might emerge.
What are AlloStim cells and how are they made?
Immunovatives pan-viral AlloPrime vaccine consists of specialized, engineered living immune cells called AlloStim. To create AlloStim cells, blood from healthy donors is collected and a subset of the white blood cells, called CD4+ T-cells, are isolated from the blood. In the laboratory, the donor T-cells are converted into a patented immune cell that is activated with antibody-coated microbeads to create AlloStim cells.
AlloStim cells possess properties from multiple types of immune cells. They have cytolytic T-cell/natural killer (NK) cell-like properties because they contain sacs (called granules) of certain digestive enzymes (perforin and granzyme B) that can destroy virally-infected cells. AlloStim cells also have the ability to promote anti-viral effects by steering the immune response to elicit Th1 helper T-cells by producing critical signaling molecules, such as CD40L, interferon-gamma (IFN-gamma), and TNF-alpha. These molecules activate macrophages, which educate the immune system to develop memory immune cells that can elicit a response upon encountering any virus.
AlloStim cells are also currently being tested in separate studies as a cancer vaccine for various chemotherapy-refractory metastatic cancers.
Weve seen that AlloStim cells provided protective effects in cancer patients with viral infections, such as lower viral counts in cancer patients with hepatitis B and lowered viral burden in HIV patients, Dr. Har-Noy said. We also have animal data demonstrating that this approach could protect mice from lethal challenge with cancer cells and malaria. These observations, in light of the current pandemic, made us think about using this technology as a preventative vaccine against viral infections.
(image above depicts AlloStim cells. Credit: Immunovative Therapeutics)
How can AlloStim cells be used as a pan-viral vaccine?
The rationale for creating this AlloStim cell-based vaccine was recently published in the Journal of Translational Medicine. Dr. Har-Noy suggests that giving older adults AlloStim cells can repopulate their exhausted immune cells, creating an army of new, refreshed memory immune cells that are ready and waiting for an invader.
Because AlloStim cells are intentionally mismatched to the person, their immune system will be alerted and create an immune response against the cells. After injecting the angry living AlloStim cells under the skin, the cells produce high levels of inflammatory molecules (such as IFN-gamma and TNF-alpha) and express CD40L on their surface. These inflammatory molecules, in addition to danger signals released by the persons own cells, cause an immune response known to be effective against most viral infections.
The elderly have missing or senescent interferon-producing cells, and many modern viruses, such as the virus that causes COVID-19, actively suppresses interferon production as an immune evasion strategy, Dr. Har-Noy said. The goal of this pan-viral vaccine is to provide this missing part of the elderly immune system to overcome the viral evasion mechanism and provide an immediate source of interferon.
Having a stronger, quicker anti-viral immune response the next time they encounter an invading virus provides heterologous immunity, tamping down the early viral infection before it can get out of hand.
Allopriming with AlloStim cells is a more refined and modern method to elicit heterologous immunity, explained Dr. Har-Noy. Heterologous immunity can broaden the protective outcomes of vaccinations, so it could potentially be used to enhance a future COVID-19 vaccine to be more effective in the elderly.
The AlloPrime vaccine wouldnt just be for healthy people either. At the onset of a viral illness, such as COVID-19, a person who previously got this vaccine could get another dose of AlloStim cells. This would prompt a stronger and faster anti-viral immune response that could help the body fight off the virus quicker.
AlloStim cells have already been shown to prompt an immune response in heavily immunocompromised cancer patients, whose immune systems are not too far off from the weakened older immune system. Although it is not known how long the AlloStim-induced immunity lasts, Dr. Har-Noy said it lasted for years in many of the cancer patients they assessed.
AlloStim cells have the benefits of having lots of human safety data and these cells are already being manufactured under good manufacturing processes (GMP), so we are able to quickly pivot into COVID-19 clinical trials, commented Dr. Har-Noy. In addition, since the AlloStim cells are off-the-shelf, where one donor can produce enough doses for potentially thousands of patients, the vaccine has the benefit of economy of scale to make it more affordable.
FDA clearance of Phase I/II study
The FDA recently cleared Immunovative and Mirror Biologics to begin a Phase I/II trial of their pan-viral AlloPrime vaccine in healthy older adults. For the study, the company aims to recruit a total of 40 healthy adults divided between two age cohorts: ages 65-74 and ages 75+.
Participants will receive five doses of the vaccine intradermally (under the skin) within a 14-day period, each dose being a few days apart. They will be monitored for adverse events for 30 days after receiving their initial dose. Blood samples will be taken before, 30 days after, 6 months after, and 1 year after initial dosing to monitor immune response durability.
The blood samples will be used to monitor participants immune response to the vaccine, including if they make memory T-cells against the AlloStim cells, if those memory T-cells can be activated after exposure to virus components, and if the activated memory T-cells can trigger an anti-viral state (if they produce IFN-gamma) and suppress viral growth in virally-infected human respiratory tract cells. The vaccine-induced cytotoxic T-cells ability to kill virally-infected cells will also be assessed.
This is a good way to show efficacy because it produces a definitive response, Dr. Har-Noy said. The production of neutralizing antibodies against the virus of interest doesnt necessarily determine a vaccines efficacy. Especially for new viral infections like COVID-19, we dont know if the antibodies recovered from patients are protective or, if they are protective, for how long they provide protection.
The Phase I/II study is expected to begin next month.
More:
A 'Pan-Viral' Vaccine Designed to Protect the Elderly from Known, and Unknown, Viruses - BioSpace
- Technion team discovers important adaptive strategy of the microbiome, impacting immune system - The Jerusalem Post - April 16th, 2024
- Targeting aging and age-related diseases with vaccines - Nature.com - April 16th, 2024
- Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic ... - Nature.com - April 16th, 2024
- After the Smoke Clears: Scars on the Immune System - The Scientist - April 16th, 2024
- Exercise and the Immune System: What's the Latest Research? - Technology Networks - April 16th, 2024
- Analysis of immune cell infiltration characteristics in severe acute pancreatitis through integrated bioinformatics ... - Nature.com - April 16th, 2024
- Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original ... - Nature.com - April 16th, 2024
- Harnessing the power of the body's own cells to defeat cancer - Press Publications Inc. - April 16th, 2024
- Best Life: Immunotherapy targets brain cancer - Action News 5 - April 16th, 2024
- Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review | Cell Death ... - Nature.com - April 16th, 2024
- New insights on B cells: Researchers explore building better antibodies and curbing autoimmune diseases - Medical Xpress - April 16th, 2024
- Immune cells' intense reaction to the coronavirus may lead to pneumonia - Science News Magazine - April 16th, 2024
- The telltale traces long Covid leaves in the blood - healthcare-in-europe.com - April 16th, 2024
- Overview of the Immune System - The Merck Manuals - March 18th, 2024
- SUNDAY Unraveling The Gut-Brain Connection: How Infant Gut Bacteria Shape Immune Resilience | TheHealthSit - TheHealthSite - March 18th, 2024
- Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics | npj Systems Biology and ... - Nature.com - March 18th, 2024
- Study unlocks the mystery of neonatal neutropenia in newborns - News-Medical.Net - March 18th, 2024
- Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic ... - Cureus - March 18th, 2024
- A new strategy to attack aggressive brain cancer shrank tumors in two early tests - ABC News - March 18th, 2024
- Turning on the Bat Signal - The Scientist - March 18th, 2024
- Power Foods That Can Support Your Immune System - Videos from The Weather Channel - The Weather Channel - March 18th, 2024
- Report: Aggressive brain tumors respond to new, immune-focused therapy - UPI News - March 18th, 2024
- Designer immune-cell therapy could shrink deadly brain tumors, early trials show - Livescience.com - March 18th, 2024
- 20.2: Introduction to the Immune System - Biology LibreTexts - February 27th, 2024
- Can one shot of yoghurt really boost your immunity and gut health? - Daily Mail - February 27th, 2024
- New cancer therapy approved by FDA supercharges bodys immune system - The Washington Post - February 27th, 2024
- How bubonic plague rewired the human immune system - BBC.com - February 27th, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Participate in Our Study for $100; Open Slots This Week - University of Arkansas Newswire - February 27th, 2024
- Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice | Scientific Reports - Nature.com - February 27th, 2024
- Comprehensive pan-cancer analysis identifies the RNA-binding protein LRPPRC as a novel prognostic and immune ... - ScienceDirect.com - February 27th, 2024
- YOUR HEALTH: The HAMR fights cancer - WAFB - February 27th, 2024
- Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat - News-Medical.Net - February 27th, 2024
- How the powerhouse of the cell could be cancers Achilles heel - Freethink - February 27th, 2024
- Food is medicine: The science behind zinc and other supplements for immune health - Healio - February 27th, 2024
- Unleashing Our Immune Response to Quash Cancer - Medscape - February 27th, 2024
- Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 ... - Nature.com - February 27th, 2024
- Converging and evolving immuno-genomic routes toward immune escape in breast cancer - Nature.com - February 27th, 2024
- Sanjula Jain Urges a Comprehensive Approach in Address Alarming Rise in Cancer Cases Among Younger Populations - Managed Healthcare Executive - February 27th, 2024
- Cystic fibrosis breakthrough points to zinc as infection buster - New Atlas - February 27th, 2024
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIVworkshop ... - Nature.com - February 27th, 2024
- Is the 100-year old TB vaccine a new weapon against Alzheimers? - The Guardian - February 27th, 2024
- Immune system in the blood of Alzheimer's patients found to be epigenetically altered - News-Medical.Net - February 10th, 2024
- What impact does exercise have on your immune system? And how to stay well while cycling - BikeRadar - February 10th, 2024
- Had COVID recently? Here's what to know about how long immunity lasts, long COVID, and more - AAMC - February 10th, 2024
- Noor Momin harnesses the immune system to treat heart disease | Penn Today - Penn Today - February 10th, 2024
- Research reveals a process tumors use to induce immune suppressor cells and evade immunotherapy - Medical Xpress - February 10th, 2024
- Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure - Nature.com - February 10th, 2024
- Preventing severe allergic reactions with nanoparticles - National Institutes of Health (NIH) (.gov) - February 10th, 2024
- Sugary handshakes are how cells talk to each other understanding these name tags can clarify how the immune ... - The Conversation Indonesia - February 10th, 2024
- Scientists have identified an immune cell that can cause allergies - EL PAS USA - February 10th, 2024
- Sickle cell and the importance of the immune system - Punch Newspapers - February 10th, 2024
- Which cancers can be treated with immune checkpoint inhibitors? - MD Anderson Cancer Center - February 10th, 2024
- How does waste leave the brain? Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis - February 10th, 2024
- Healthy Kids: Give your immune system a boost to stay healthy this winter - nbc16.com - February 10th, 2024
- The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode ... - Cardiovascular Diabetology - February 10th, 2024
- Impact of Chronic Stress on Immune System and Depression | Health News - Medriva - February 10th, 2024
- I tried 'swamp soup,' the viral recipe that promises to boost your immune system - Yahoo News - February 10th, 2024
- Understanding Immune Checkpoint Inhibition Therapy: Challenges and Strategies - Medriva - February 10th, 2024
- One Simple Change May Dramatically Boost The Effect of COVID-19 Vaccines - ScienceAlert - February 10th, 2024
- The gut virome is associated with stress-induced changes in behaviour and immune responses in mice - Nature.com - February 10th, 2024
- Cancer vaccines are in the works to fight BRCA-linked gene mutations - The Philadelphia Inquirer - February 10th, 2024
- What are the organs of the immune system? - InformedHealth.org - NCBI ... - January 17th, 2024
- Novel insights into the immune response to bacterial T cell superantigens - Nature.com - January 17th, 2024
- FDA signs off on Takeda's HyQvia as maintenance therapy for CIDP - FiercePharma - January 17th, 2024
- CBDs Pobezinsky and Pobezinskaya Use Flow Cytometry to Determine How Tumor Cells Outwit the Bodys Immune ... - UMass News and Media Relations - January 17th, 2024
- Boosting. What To Do. - Science Based Medicine - January 17th, 2024
- Axelia Oncology takes its TLR2/6 agonist into the clinic to harness the innate immune system - BioWorld Online - January 17th, 2024
- Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to ... - Nature.com - January 17th, 2024
- Opinion | Thanks to mRNA, Future Drugs Will Be Easier and Faster to Make - Mississippi Free Press - January 17th, 2024
- Elon research team models the COVID immune response, one equation at a time - Today at Elon - January 17th, 2024
- Are plant-based meals good for your immune system? 4 things to know about improving your health this week. - Yahoo Life - January 17th, 2024
- Scientists Find Key To Potential Breast Cancer Prevention, Treatment | Newsroom - UNC Health and UNC School of Medicine - January 17th, 2024
- What if every germ hit you at the exact same time? An immunologist explains - The Conversation - January 17th, 2024
- Why Don't We Have a Staph Vaccine? - Healthnews.com - January 17th, 2024
- Best ways to improve your immune system - The Business Standard - January 17th, 2024
- Stanford University researchers think future pandemics could be prevented with universal vaccines - KGO-TV - January 17th, 2024
- Why you may feel depressed and anxious when you're ill and how to cope with it - The Conversation - January 17th, 2024
- New mechanism with potential to boost checkpoint-blocking cancer immunotherapies identified - Medical Xpress - January 17th, 2024
- Battling Bugs and Blues: The Interplay of Infection and Emotion - News-Medical.Net - January 17th, 2024