Historic diabetes treatment focuses on treating the condition with insulin. However, recent immunotherapies move towards the potential to delay or prevent type 1 diabetes (T1D). Provention Bio, Inc. is a biopharmaceutical company focused on the interception and prevention of immune-mediated disease.* In March 2022 they announced positive results in their first in-human study of PRV-101, a coxsackievirus B (CVB) vaccine that addresses all key strains associated with T1D. CSO and co-founder Dr Francisco Leon describes these results as “incredibly exciting”.
So, what are the links between CVB and diabetes, and how is a vaccine going to disrupt them? CVB is common but serious, and damages insulin-producing and gut-lining cells. It can trigger autoimmune damage to the pancreatic beta cells, sometimes leading to T1D and intestinal damage that can cause celiac disease. CVB was identified in the pancreas of around 60% of patients with T1D.
Dr Jeffrey Almond of the University of Oxford stated that the “causal link between CVB infection in childhood and the onset of T1D is compelling”. PRV-101 is polyvalent vaccine that is specifically designed to prevent a putative infectious trigger, and data thus far suggests that it “induced high neutralising antibody titres against CVBs”, said Dr Heikki Hyoty of Tampere University.
Diamyd Medical are also developing a type 1 vaccine to “reprogram the immune system”, according to CEO Ulf Hannelius. He describes the objective as changing the “pro-inflammatory, autoimmune reaction to GAD-65″ to an anti-inflammatory reaction. In the US the trial is on “partial clinical hold” as the FDA reported insufficient information on the drug. Hannelius stated that Diamyd would “treat the FDA’s questions with the highest priority”. On May 19th 2022 Diamyd announced that a new phase III trial was beginning across several European countries with the ambition of including around 330 participants.
Researchers inject small amounts of the GAD-65 protein into a lymph node; the intention is for these immune cells to migrate to the pancreas and preserve, instead of attack, beta cells with GAD-65. This administration sees a “stronger immune response” than subcutaneous injections. Data are promising, revealing ameliorated glucose management compared to the placebo group. In July 2022 Diamyd announced further results from a 14-person study and will expand on these in the EASD 2022 in September. The expectation is that the Diamyd vaccine might become a therapeutic solution that would combat the immune response that leads to T1D and prevent further complications.
As an estimated 8% of the British population currently live with type 1 diabetes these developments present an opportunity to manage or prevent the multitude of life-altering consequences that T1D brings.
*To hear Dr Miguel Sanjuan of Provention Bio at the World Vaccine Congress Europe in October 2022 secure your tickets here.
In March 2024 Nykode Therapeutics announced “key updates” to the inverse vaccine platform with the potential to treat autoimmune diseases at a conference in the US. During the event, Nykode “demonstrated for the first time” a “significant effect” in a therapeutic setting in a preclinical model for Multiple Sclerosis (MS) with the inverse vaccine platform.
The data shared at the conference also “illustrate the strong contribution” of the specific targeting unit and confirm that the disease protection is antigen-specific, which highlights the potential that the technology has in the autoimmune diseases field.
The next step in Nykode’s technology
Dr Agnete Fredriksen, Chief Business Officer and Co-founder of Nykode, commented that “demonstrating effect in a therapeutic setting has been the next important step for Nykode”.
“In addition to stopping the disease development, the data show that the disease protection is antigen-specific. This supports our technology’s potential to offer future treatments that precisely target specific autoimmune disorders without negatively affecting a fully functional immune system, a common side effect associated with today’s available treatments.”
The results bring “additional motivation” for Dr Fredriksen’s team to “pursue a completely new approach” to the treatment of autoimmune diseases. These “affect around every tenth person globally”, says Dr Fredriksen. In September 2023, Nykode announced that the inverse vaccine platform had prevented serious disease in MS and type 1 diabetes models in mice, which showcased the “broad disease-modifying potential in an antigen-specific manner”.
With just a few weeks left until the World Vaccine Congress in Europe 2022 we are looking forward to hearing from a range of incredible speakers. One such speaker is Dr Miguel Sanjuan, SVP Research and Development at Provention Bio. He will be showcasing a vaccine candidate PRV-101. We spoke to him ahead of his showcase to learn a little more about what we can expect, and what work is still to be done.
What is PRV-101?
Without giving too much away, we asked Dr Sanjuan if he could hint at what we might hear in Barcelona. He told us that Provention is “researching the safety and immunogenicty of our investigational candidate, PRV-101 for the prevention of acute CVB infection”. Furthermore, its “potential for preventing autoimmune disorders that are driven by latent CVB infection” is considered. PRV-101 is a “polyvalent inactivated coxsackievirus B (CVB) vaccine candidate”. It targets “all key CVB strains”. So far it has “met its primary endpoint in a Phase I, first in-human trial”.
Clarifying that PRV-101 is “not approved for any use at the present time”, Dr Sanjuan stated that there is “a lot of development” needed before we will see “benefits to the market or to the community”. However, this progress is exciting. Dr Sanjuan outlined the importance of targeting CVB.
“Acute infection can cause myocarditis, meningitis, pericarditis, otitis, and hand-foot-mouth disease. Recent research strongly supports that CVB also damages insulin-producing cells and gut-lining cells causing autoimmunity.”
In his presentation, Dr Sanjuan will discuss data from an initial Phase I study. As well as meeting the safety primary endpoint, this vaccine produced immunogenicity results that suggest it is worth studying in connection with “blocking acute CVB infection” and “the prevention of autoimmune disorders associated with latent CVB infection”.
Dr Sanjuan referred to a “substantial body of evidence” pointing to the role of CVB as a “trigger in the initiation of two common autoimmune diseases”. These are Type 1 Diabetes (T1D) and Coeliac Disease. As well as the “acute consequences of CVB infection, vaccines for CVB may potentially prevent CVB-driven autoimmunity”.
So why PRV-101, and what is next?
When we asked what the vaccine offered that is unique in comparison with other programmes, Dr Sanjuan reflected that PRV-101 is, to his knowledge, the “only vaccine in development against key relevant CVB viruses”. He believes there isn’t another polyvalent CVB vaccine in development.
“That makes PRV-101 unique, fully differentiated from other programmes in development, and provided it proves to be efficacious in the future, a potential first in class.”
The next steps for the vaccine will be “investigating the dose and safety” in children. If the researchers can establish an “acceptable safety profile in a paediatric population” they may be able to advance to a “larger proof of concept trial”. This would explore whether PRV-101 can prevent acute infection and CVB-mediated T1D.
Autoimmune vaccines
We recognise that public understanding of vaccines for the treatment of autoimmune disorders is limited. Therefore, we asked Dr Sanjuan what he hopes to make clear at the Congress and beyond. He identified the “emerging evidence that latent viral infection can drive autoimmunity”. The connection between EBV and multiple sclerosis has been “known for several years”. Similarly, and “according to literature”, Dr Sanjuan stated that “CVB is the only virus on the human virome whose persistent infection is significantly associated with the development of T1D and coeliac disease on patients with predisposed genetic risk”.
Clinical mouse models “clearly show that vaccination against CVB prevents autoimmune diabetes”. Dr Sanjuan’s message for the public, therefore, is that vaccines play a role in “preventing the acute consequences of viral infections”, but could also play a role in preventing autoimmunity. He recognises that, because of the COVID-19 pandemic, “public awareness of vaccinations as an important part of family and public health has significantly increased”.
“Vaccines can be cost-effective treatments and government and private capital have now a renewed interest on being more strategic and proactive in developing vaccines for the treatment of old and new infective agents.”
Despite this, the importance of researching vaccines “spans beyond fighting infections”. For example, cancer antigens in vaccines have proven “promising” in treatment. Provention Bio is developing autoimmune vaccines. The effect of this treatment, if successful, could be “substantial”. Dr Sanjuan cites the number of more than 300,000 people in the US who are in the early stages of T1D at “any given time”.
“A successful CVB vaccine could potentially prevent CVB infection but also up to ~50% of T1D and ~20% of coeliac disease.”
Challenges and changes
We asked Dr Sanjuan about public health work and the relationship between the scientific community and public opinion. He believes that there is a tension between public recognition that “scientific research supports the advancement of novel treatments” and “reservations about warning of an impending public health crisis”. The key to “breaking through this scepticism” is “education”. He very graciously identified the Congress as a “critical” player in the mission!
“As one of the most well-regarded vaccine meetings, it brings together global experts creating a unique opportunity to discuss the state of research and development of vaccines but also to educate the public on our latest understanding of threats and research on potential treatments.”
When we reflected on technological advancements, Dr Sanjuan pointed out that the past decade has allowed disciplines such as “translation research” to “deliver on the promise of understanding deeply the pathophysiological mechanisms of disease”. He is interested in taking this on board to “develop novel therapies that intercept disease before they lead to irreversible damage and organ failure”. His example of individuals who discover they have T1D “the same day they need to start insulin treatment” emphasised this need.
With the help of genetic biomarkers “we now know that patients can be tested to determine whether they are at increased risk of developing symptomatic disease”. These patients “could benefit from vaccines or therapies for early-stage T1D”. However, this is “different to treating the disease at its chronic stage and when the damage has already occurred”.
“At Provention, we are committed to therapies that intercept and prevent autoimmune disease ahead of irreversible tissue damage.”
For those of us lucky enough to hear Dr Sanjuan’s presentation, we will hear more about the promise of developing a CVB vaccine and the initial safety data for PRV-101 .
Hope for the future
We concluded our interview by looking to the future and public health threats. Dr Sanjuan referred to the WHO’s warning that “noncommunicable diseases, such as diabetes, cancer, and heart disease are collectively responsible for over 70% of all deaths worldwide”. Furthermore, they are “responsible for the premature death of more than 15 million people globally”.
“It is therefore encouraging that vaccines that typically represent safe and cost-effective options are being developed for the treatment of some of those serious diseases.”
We thank Dr Sanjuan for his time and the thought he put into these answers ahead of his appearance at the Congress in October. We look forward to hearing more from him at the showcase! If you would like to join us, make sure you get your tickets here.
In January 2024 the University of Oxford announced that the Jenner Institute is conducting a new study using the current licensed vaccine against tuberculosis. The Jenner Institute states that there is interest in considering a “booster” dose of BCG, which is “not always protective”. The study will involve administration of the vaccine for a second time to people who have already had it once before, allowing a comparison of whether inhalation provides greater protection than injection into the skin.
An urgent need
Professor Helen McShane, Chief Investigator, commented that “TB kills more people than any other infectious disease” and we “urgently need better vaccines”.
“This important new study will help us to see whether giving BCG more than once stimulates a stronger immune response and whether giving it by inhalation is better than giving it into the skin.”
The study is “really important” for enabling better understanding of the immune response and facilitating the design and testing of better vaccines. The study will also explore the difference between administration of BCG to the skin stimulates as strong an immune response in people with type 2 diabetes as in people without diabetes.
“We know that people with type 2 diabetes are more likely to get TB and part of this may be because the BCG vaccine does not work as well in this group.”
The investigation involves healthy volunteers, both with and without type 2 diabetes, who have previously been vaccinated with BCG. The cohort will be divided into 3 groups of 12 volunteers.
Dr Aye Thu, Clinical Research Fellow at the Centre for Clinical Vaccinology and Tropical Medicine reflected that “despite BCG vaccine being around for more than 100 years, tuberculosis remains the leading cause of death from an infectious cause”. Once patients are infected with TB, a “significant proportion of the population” continue to get sick or die “even with TB medication”.
“Having a new way of optimising the BCG vaccine will ultimately improve the health of people all over the world. This study will give the participants an opportunity to get involved in testing an exciting new way of delivery BCG vaccine through the aerosol route.”
