There are several promising new vaccine candidates being developed for complex diseases that historically have been extremely 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 able to prevent more than 20 life-threatening diseases, in turn preventing 3.5 to five million deaths every year from diseases such as diphtheria, tetanus, influenza and measles.
Vaccines are designed to trigger an immune response to help the body fight off infections. Traditionally, vaccines contain weakened or inactive forms of a particular bacteria or virus to help trigger an immune response, but more recent vaccines use molecules called messenger RNA (mRNA) containing instructions that direct cells to make a protein that then triggers an immune response.
And, while vaccines have traditionally been used as a preventative measure, newer vaccines – known as ‘therapeutic vaccines’ – can potentially treat an illness even after patients have it.
Given the advancements in technology for developing vaccines, it’s no wonder that they are now being tried and tested for the treatment of more complex diseases, such as Alzheimer’s, HIV, Parkinson’s, and Lyme disease. In this article, we explore six new vaccines in clinical development for difficult-to-treat diseases.
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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, despite more than 55 million people living with Alzheimer’s and other forms of dementia.
Biotech company Vaxxinity is hoping to change that with its UB-311 vaccine candidate for Alzheimer’s, which targets toxic forms of aggregated amyloid beta in the brain. Amyloid beta is the predominant pathologic protein in Alzheimer’s, which clump together to form plaques, collecting between neurons and disrupting 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 repeat dosing. The safety profile was demonstrated to be comparable to placebo, and there were no cases of amyloid-related imaging abnormalities-edema (ARIA-E) in the phase 2a main study.
“UB-311 also elicited robust and durable anti-amyloid beta antibody responses in patients, and we have observed trends of approximately 50% slowing of cognitive and functional decline as measured by 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 fast track designation from the U.S. Food and Drug Administration (FDA) in the second quarter of 2022.
Hu said the company expects to continue the development of the Alzheimer’s vaccine with a strategic partner, focusing on initiation of a pivotal trial supporting licensure.
IAVI G001 and IAVI G003 trials: Vaccine for HIV
The unprecedented genetic variability of the virus and its ability to cause a lifelong infection, along 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 nonprofit research organization, and Moderna are now trying to develop a vaccine to combat the HIV virus, which makes use of Moderna’s mRNA platform.
Researchers developing the investigational vaccine are using a strategy known as ‘germline targeting’ to produce broadly neutralizing antibodies (bnAbs) – a rare type of antibody that can fight and protect against many different variants of a virus – which can protect against HIV.
Germline targeting involves stimulating the rare immune cells known as bnAb-precursor B cells, which can eventually evolve into cells that produce the bnAbs needed to block the virus. To accomplish this, researchers designed an immunogen that can prime the immune system and elicit responses from the bnAb-precursor cells.
The phase 1 trial for the vaccine, known as IAVI G001, tested the first stage in a multi-stage HIV vaccine regimen. The results were promising and showed that the HIV vaccine had a favorable safety profile and induced the targeted response in 97% of people who received the vaccine.
Another trial, IAVI G003, also began in May 2022, which is designed to test whether the vaccine candidate can induce similar immune responses in African populations as were seen in the IAVI G001 trial.
ACI-7104: Vaccine for Parkinson’s disease
Targeting the protein alpha-synuclein is a common approach when developing treatments for Parkinson’s disease, due to the fact that the disorder is associated with Lewy bodies, which are protein deposits in the brain composed of accumulated alpha-synuclein. The protein is known to misfold and aggregate into clumps in Parkinson’s.
AC Immune’s ACI-7104 also takes this approach, with the vaccine in development targeting the harmful alpha-synuclein protein by generating an antibody response against pathological oligomeric alpha-synuclein to inhibit spreading and downstream neurodegeneration in early Parkinson’s.
The vaccine candidate was acquired from biopharmaceutical company Affiris, when, in 2021, AC Immune announced it was acquiring Affiris’ portfolio of therapeutics targeting alpha-synuclein, which included Affitope PD01A – Affiris’ clinically-validated active vaccine candidate for the treatment of Parkinson’s.
The results of a randomized phase 1 trial of PD01A showed that the Parkinson’s vaccine in development generated substantial, long-lasting and boostable antibody responses against pathological forms of alpha-synuclein that were accompanied by target engagement and signals of clinical efficacy.
“We started out with a clinically validated product candidate, which we are now taking into phase 2. Now, we did repeat quite a few studies because when you acquire a product, it’s very important that you have full confidence and that your basis is clear. So, we repeated many of the data and it was very, very good, and we manufactured the product, we went to different countries for regulatory approval, and we got all of this,” said Andrea Pfeifer, co-founder and CEO of AC Immune.
Now, AC Immune is waiting to announce the dosing of the first patients in its phase 2 trial of the Parkinson’s vaccine candidate, and expects to potentially have the first immunogenicity data by the end of this year if everything 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), having been initiated in August 2022. The study is assessing the efficacy, safety, tolerability and immunogenicity of the vaccine in participants five years and older.
Lyme disease is the most common vector-borne disease in the Northern Hemisphere, and is caused by Borrelia burgdorferi bacteria, which is transmitted to humans by infected Ixodes ticks.
The Lyme vaccine candidate, being 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 is targeting six serotypes of the bacteria.
The VALOR study is taking place over 29 months. During the first year of the 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 the primary immunization.
The Lyme disease vaccine candidate received a fast track designation from the FDA in 2017, and – pending successful completion of the phase 3 study – Pfizer could potentially submit a Biologics License Application (BLA) to the FDA, and Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2025.
HER2 DNA study: Vaccine for breast cancer
There is a lot of work being done at the minute surrounding the development of cancer vaccines, and researchers from the University of Washington School of Medicine in Seattle, U.S., are working on developing a vaccine for breast cancer, which is difficult to treat due to the fact there are many types of breast cancer, and treatments that work well for some people might not necessarily work for others.
The investigational vaccine is a DNA vaccine that targets the HER2 protein that is found at abnormally high levels and is thought to be the cause of the disease in 20% to 30% of patients with breast cancer.
These types of breast cancers are called HER2 positive. In these types of cancers, HER2 is overproduced by as much as one hundred times the amount seen in normal cells, and HER2 positive cancers are generally more aggressive and more likely to occur after treatment. However, the high levels of HER2 can trigger a beneficial immune reaction.
“The goal of the vaccine is to train the patient’s immune system to recognize the HER2 protein on cancer cells as dangerous and then mount an immune response to destroy the cancer cells,” said Kiran Dhillon, executive director of the Cancer Vaccine Institute at the University of Washington.
“We give the vaccine by giving patients three shots one month apart, with a piece of DNA that codes for segments of the HER2 protein we know can cause the immune system to have a strong response. In this study, we looked at three different doses of the vaccine in a total of 66 patients with advanced stage breast cancer that was HER2 positive.”
The phase 1 study found that: the breast cancer vaccine candidate in development is safe, with only mild side effects; all three doses elicited an immune response; and 80% of patients who received the median dose, as well as 70% of patients who received the lower and higher doses, are still 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 also HSV-1, both of which have always been difficult to treat and for which there are currently no cures.
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 of clinical development, with the first patient having been dosed in December 2022.
According to the company, the trial is expected to enroll around 100 healthy volunteers aged 18 to 55 in the U.S. who don’t have a current history of symptomatic genital herpes infections. The study consists of a first dose escalation part that will focus on safety evaluations and assess the optimal dose-response in various dose levels.
Meanwhile, the second part of the trial will expand the safety characterization for the selected dosing, in order to more comprehensively assess the impact of pre-existing immunity to both HSV-1 and HSV-2 on the safety and BNT163-induced immune responses.
BNT163 is an mRNA-based vaccine that encodes three HSV-2 glycoproteins to help prevent HSV cellular entry and spread and counteract the immunosuppressive properties of HSVs.