6 new vaccines in development for difficult-to-treat diseases

There are several promising new vaccine candidates under development for complex diseases that have historically been very difficult to find treatments and cures for. The development of these new vaccines could eventually lead to breakthrough treatments for diseases such as Alzheimer’s disease, HIV, Parkinson’s disease, Lyme disease and breast cancer.

According to the World Health Organization (WHO), currently available vaccines are capable of preventing more than 20 life-threatening diseases, in turn preventing 3.5 to five million deaths each year from diseases such as diphtheria, tetanus, influenza and measles.

Vaccines are designed to trigger an immune response to help the body fight infection. Traditionally, vaccines contained weakened or inactivated forms of certain bacteria or viruses to help trigger an immune response, but newer vaccines use molecules called messenger RNA (mRNA) that contain instructions that direct cells to make proteins that then trigger an immune response.

And, while vaccines have traditionally been used as a preventative measure, newer vaccines – known as ‘therapeutic vaccines’ – can potentially treat disease even after patients have had it.

Given advances in technology for developing vaccines, it is not surprising that they are now being tried and tested for the treatment of more complex diseases, such as Alzheimer’s disease, HIV, Parkinson’s and Lyme disease. In this article, we explore six new vaccines in clinical development for difficult-to-treat diseases.

UB-311: Vaccine for Alzheimer’s disease

Alzheimer’s disease is notoriously difficult to treat, and is the most common cause of dementia. It is a neurodegenerative disorder for which there is currently no cure, although more than 55 million people are living with Alzheimer’s and other forms of dementia.

Biotechnology company Vaxxinity hopes to change that with its UB-311 vaccine candidate for Alzheimer’s, which targets a toxic form of amyloid beta-aggregates in the brain. Amyloid beta is the main pathological protein in Alzheimer’s, which clumps to form plaques, collects between neurons and interferes with cell function.

In phase 1, phase 2a, and phase 2a long-term extension trials, the vaccine candidate was shown to be well tolerated in patients with mild to moderate Alzheimer’s disease over three years of repeated dosing. The safety profile proved comparable to placebo, and there were no cases of amyloid-edema-associated imaging abnormalities (ARIA-E) in the main phase 2a study.

“UB-311 also elicited a strong and long-lasting anti-amyloid beta antibody response in patients, and we have observed a trend of approximately 50% slowing of cognitive and functional decline as measured by the CDR-SB, ADCS-ADL, and ADAS-Cog,” said Mei Mei Hu, chief executive officer (CEO) of Vaxxinity.

The vaccine candidate for Alzheimer’s disease also received a fast-track designation from the US Food and Drug Administration (FDA) in the second quarter of 2022.

Hu said the company expects to continue developing an Alzheimer’s vaccine with strategic partners, focusing on initiating important trial support licenses.

The IAVI G001 and IAVI G003 trials: Vaccines for HIV

The unprecedented genetic variability of the virus and its ability to cause lifelong infection, together with the fact that the body has never been shown to clear the virus on its own, makes HIV extremely difficult to treat in terms of finding a cure for the disease. .

But IAVI, a non-profit research organization, and Moderna are now trying to develop a vaccine against the HIV virus, which takes advantage of Moderna’s mRNA platform.

Researchers developing investigative vaccines use a strategy known as ‘germline targeting’ to produce broadly neutralizing antibodies (bnAbs) – rare types of antibodies that can fight and protect against many variants of the virus – that can protect against HIV.

Germline targeting involves stimulating rare immune cells known as bnAb precursor B cells, which may eventually develop into cells that produce the bnAb needed to block viruses. To achieve this, the researchers designed an immunogen that can strengthen the immune system and elicit a response from bnAb precursor cells.

The phase 1 trial for the vaccine, known as IAVI G001, is testing the first stage in a multi-stage HIV vaccine regimen. The results are promising and show that the HIV vaccine has a favorable safety profile and induces a targeted response in 97% of people who receive the vaccine.

Another trial, IAVI G003, also starting in May 2022, is designed to test whether the vaccine candidate can induce a similar immune response in African populations as seen in the IAVI G001 trial.

ACI-7104: Vaccine for Parkinson’s disease

Targeting the alpha-synuclein protein is a common approach when developing treatments for Parkinson’s disease, due to the fact that the disorder is linked to Lewy bodies, which are protein deposits in the brain that consist of alpha-synuclein accumulations. The protein is known to misfold and clump together in Parkinson’s.

ACI-7104 from AC Immune also takes this approach, with a vaccine under development targeting the harmful alpha-synuclein protein by generating an antibody response to pathological oligomeric alpha-synuclein to inhibit the spread and decrease neurodegeneration in early Parkinson’s.

The vaccine candidate was obtained from the biopharmaceutical company Affiris, when, in 2021, AC Immune announced the acquisition of the Affiris portfolio of therapies targeting alpha-synuclein, including Affitope PD01A – Affiris’ active vaccine candidate clinically validated for the treatment of Parkinson’s.

Results of the randomized phase 1 trial PD01A demonstrated that the Parkinson’s vaccine under development produces a substantial, long-lasting, and boostable antibody response against the pathological form of alpha-synuclein accompanied by target engagement and clinical efficacy signals.

“We started with a clinically validated product candidate, which we are now taking to phase 2. Now, we are repeating some of the research because when you get a product it is very important that you have complete trust and your foundations are clear. . So, we looped through a lot of data and it was very, very good, and we built the product, we went to different countries for regulatory approvals, and we got all of this,” said Andrea Pfeifer, co-founder and CEO of AC. Immune.

Now, AC Immune is waiting to announce the first patient dose in a phase 2 trial of its Parkinson’s vaccine candidate, and hopes to potentially have the first immunogenicity data by the end of this year if all goes according to plan.

VLA15: Vaccine for Lyme disease

VLA15 is the only Lyme disease vaccine candidate currently in advanced clinical development, with a phase 3 study, VALOR (Vaccine Against Lyme for Outdoor Recreationists), starting in August 2022. This study assessed the efficacy, safety, tolerability, and immunogenicity of vaccine in participants five years of age and older.

Lyme disease is the most common vector-borne disease in the Northern Hemisphere, and is caused by Borrelia burgdorferi bacteria, which are transmitted to humans by infected Ixodes ticks.

The Lyme vaccine candidate, co-developed by Valneva and Pfizer, is a multivalent protein subunit vaccine that uses an established mechanism of action to target the outer surface protein A of B. burgdorferi. It targets six bacterial serotypes.

The VALOR study spanned 29 months. During the first year of study, as part of the primary series, participants will receive three doses of VLA15, before receiving one booster dose approximately one year after completion of primary immunization.

That Lyme disease vaccine candidate received fast-track designation from the FDA in 2017, and – pending successful completion of phase 3 studies – Pfizer could potentially submit a Biological Licensing Application (BLA) to the FDA, and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2025 .

HER2 DNA studies: Vaccines for breast cancer

There is a lot of work currently being done around developing a cancer vaccine, and researchers from the University of Washington School of Medicine in Seattle, USA, are working on developing a vaccine for breast cancer, which is difficult to treat due to the fact that there are many types of breast cancer, and treatments that work well for some people it may not work for others.

The investigational vaccine is a DNA vaccine that targets the HER2 protein which is found at abnormally high levels and is thought to cause disease in 20% to 30% of breast cancer patients.

This type of breast cancer is called HER2 positive. In this type of cancer, HER2 is overproduced to a hundred times the amount seen in normal cells, and HER2 positive cancers are generally more aggressive and more likely to occur after treatment. However, high HER2 levels can trigger beneficial immune reactions.

“The goal of this vaccine is to train a patient’s immune system to recognize the HER2 protein on cancer cells as harmful and then mount an immune response to destroy those cancer cells,” said Kiran Dhillon, executive director of the University’s Cancer Vaccine Institute. from Washington.

“We give the vaccine by giving three injections to patients one month apart, with a piece of DNA that codes for a segment of the HER2 protein that we know causes the immune system to have a strong response. In this study, we looked at three different vaccine doses in a total of 66 HER2-positive, advanced breast cancer patients.”

The phase 1 study found that: the breast cancer vaccine candidate being developed was safe, with only mild side effects; all three doses elicit an immune response; and 80% of patients who received the average dose, as well as 70% of patients who received the lower and higher doses, were alive 10 years after vaccination.

BNT163: Vaccine for herpes simplex virus 2 (HSV-2)

BNT163 is a vaccine candidate being developed by BioNTech for HSV-2 – also known as genital herpes – and potentially HSV-1, both of which have always been difficult to treat and currently have no cure.

The vaccine is the first candidate from BioNTech’s infectious disease mRNA vaccine collaboration with the University of Pennsylvania to enter the clinic, and is currently in phase 1 clinical development, with the first patient dose to have been administered in December 2022.

According to the company, the trial is expected to include about 100 healthy volunteers ages 18 to 55 in the US with no history of symptomatic genital herpes infection. The study comprises a first dose escalation section that will focus on evaluating safety and assessing optimal dose response across various dose levels.

Meanwhile, the second part of the trial will expand the safety characterization for selected doses, to more comprehensively assess the impact of preexisting immunity to HSV-1 and HSV-2 on safety and BNT163-induced immune response.

BNT163 is an mRNA-based vaccine that encodes three HSV-2 glycoproteins to help prevent HSV cellular entry and spread and counteract HSV’s immunosuppressive properties.