In April 2023 Ultimovacs ASA announced that it has adjusted guidance for communication of top-line data from early 2023 to later in the year. A statement from the company indicated that this was due to slow disease progression in patients. However, it is uncertain to what extent the vaccine was contributing to this delay.
UV1 is a universal cancer vaccine designed to induce a specific T cell response against human telomerase (hTERT). It comprises long, synthetic peptides, which represent a sequence in the reverse transcriptase subunit hTERT, shown to induce CD4+ T cells. These cells can provide inflammatory signals and support believed to be “critical for triggering a strong anti-tumour” response.
Ultimovacs states that, following intradermal injection, antigen presenting cells (APCs) in the skin are exposed to the vaccine peptides. The APCs process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T cells in the lymph nodes. Activated vaccine T cells will then enter the circulation and identify cells displaying their cognate antigen in the context of HLA molecules.
The vaccine is administered over 3 months as 8 injections alongside the immune-modulator GM-CSF. It is being investigated in the INITIUM trial, a comparative, randomised Phase II trial for first-line treatment of patients with advanced or metastatic malignant melanoma. Enrolment began in June 2020 and was completed in June 2022 with 156 patients.
An encouraging sign
CEO of Ultimovacs, Dr Carlos de Sousa, is “encouraged”. Disease progression is “slower than anticipated” in comparison with “historical data”.
“This is positive for patients, though we do not know if UV1-related efficacy is responsible for this extended time to expected readout since both Ultimovacs and the investigators remain blinded.”
Dr de Sousa looks forward to “learning to what degree UV1 may have contributed to the clinical outcome for patients”.
INITIUM has an “event-driven design”, resulting in top-line progression free survival results being disclosed after progression or death has been verified in 70 patients. Historical data for a combination of ipilimumab and nivolumab indicated that this progression might occur by the first half of 2023. However, it is taking “longer than anticipated” to observe this progression in the required number of patients. Thus, the top-line results will not be announced before the second half of 2023.
For more on therapeutic vaccine efforts against cancer head to our therapeutic section or subscribe for updates in your inbox each week.
Allergy Therapeutics announced in April 2023 that the first cohort of patients with peanut allergies had “successfully” taken the “innovative short-course peanut allergy vaccine candidate”, VLP Peanut through skin prick testing (SPT). Through the PROTECT trial, the first-in-human study to evaluate VLP Peanut in adult subjects, the company aims to establish safety and tolerability.
Peanut allergies increase
Allergy Therapeutics suggests that peanut allergy is one of the most common types of food allergies, with symptoms ranging from mild to severe or even life threatening. An observed increase in peanut allergies is cause for concern, with around 2% of children in the UK affected. Although it most commonly occurs in early childhood, it can develop later in life, and only an estimated 1 in 5 children outgrow their allergies.
For the US, peanut allergies affect around 1.2% of the total population. The statement from Allergy Therapeutics suggests that 1 in 4 children with a peanut allergy require a hospital visit every year. Manuel Llobet, CEO of Allergy Therapeutics, describes the “increasing prevalence” of this “potentially life-threatening reaction”, calling for solutions “now more than ever”.
“We need better treatment options beyond the current approaches that require repeated and long-lasting exposure, therefore limiting patient adherence, and not providing sustained protection after stopping treatment.”
The open label phase of the PROTECT trial has demonstrated a “strongly reduced skin testing reactivity” of VLP peanut compared to a peanut extract, enabling the team to move to the second part of Phase I. This involves healthy subjects receiving doses of the candidate.
The vaccine candidate uses novel virus-like particle (VLP) technology to enhance the body’s immune response by likening the peanut allergen to an inactive virus. It is based on immunologically optimised cucumber mosaic virus derived VLPs with the major peanut allergen (Arachis hypogaea) displayed on the surface. Allergy Therapeutics states that this is a “step change” in allergy treatment.
“This engineered, plant-based virus, is designed for enhanced safety and provides a platform to induce protective antibodies without replicating or infecting human cells, similar to classic vaccination.”
For the growing number of people who experience a peanut allergy this could be a game changer.
Moderna announced in April 2023 that the mRNA-4157/V940, which had been granted BTD by the US FDA in February 2023, has been awarded Priority Medicines (PRIME) scheme designation by the EMA. The investigational personalised mRNA cancer vaccine is intended for combination use with Merck’s KEYTRUDA, an anti-PD-1 therapy. This combination treats patients with high-risk stage II/IV melanoma after complete resection.
Positive results lead to PRIME designation
As we reported in December 2022, Moderna and Merck shared positive results from a Phase IIb trial. The combination therapy demonstrated a “statistically significant and clinically meaningful improvement” on KEYTRUDA alone. As a result, the FDA granted Breakthrough Therapy Designation in February 2023.
PRIME is a mechanism by the EMA to provide support for medicines that target an unmet medical need. This support is described by Moderna as “early and proactive”, to optimise the generation of “robust data” and “speed up the development” of the medicine. The next steps will be discussions of the data with regulatory authorities and a plan to initiate a Phase III study this year.
Dr Stephen Hoge is Moderna’s President. He described the “high unmet need for therapies in melanoma”, which “can be a life-threatening condition” in which current therapies “may not be sufficiently effective” for many patients.
“PRIME scheme designation for mRNA-4157/V940 in combination with KEYTRUDA highlights the potential promise of individualised cancer treatments in a population with limited alternatives.”
Dr Eric H. Rubin, Senior Vice President, global clinical development, at Merck Research Laboratories, agrees that the “milestone underscores the potential” for “personalised approaches” to contribute to the improvement of outcomes for people with “certain types of melanoma”.
“We look forward to working with the EMA, in collaboration with Moderna, to advance our clinical development programme.”
Join us at the World Vaccine Congress in Europe this year for more on cancer and immunotherapy vaccine approaches.
In March 2023, Vaccitech announced top-line interim data from a Phase Ib/II clinical trial of its VTP-200 vaccine in women with low-grade cervical human papillomavirus (HPV) lesions. The vaccine is intended to treat HPV infections, catching them before the virus causes high-grade lesions. The data was described as a “promising step” with more to come in early 2024.
Vaccitech states that an estimated 291 million women across the world are “carriers” of HPV DNA. Persistent genital HPV infection is “responsible for almost all cases of cervical pre-cancerous lesions”, which can lead to cervical carcinoma.
“Over 95% of cervical cancers are caused by HPV infection.”
WHO indicates that the two most common “high-risk” genotypes cause around 70% of all cervical cancerrs.
“HPV was estimated to cause almost half a million cases and 250,000 deaths from cervical cancer in 2002.”
Although there are two prophylactic vaccines against HPV, it continues to cause problems globally.
HPV001 and VTP-200
HPV001 is a fully-enrolled, randomised, placebo-controlled multi-centre trial to evaluate the safety, efficacy, and immunogenicity of VTP-200. The study consists of an “open label, non-randomised, dose escalation lead-in phase of 9 participants”. This is followed by a “blinded, randomised main phase of approximately 96 participants with high-risk HPV”.
VTP-200 is a “investigational heterologous prime boost immunotherapy” comprising an initial dose using the ChAdOx vector and a second dose using MVA. Both encode the same HPV antigens to elicit an immune response to HPV.
Data from the first 58 women enrolled who reached their 6-month timepoint in the study were reviewed with the trial expected to continue as planned to the 12-month endpoint. Immunogenicity results showed “high responses”. This was defined by Vaccitech as an “average greater than 1,000 spot-forming units per million peripheral blood mononuclear cells in an ELISPOT assay”.
VTP-200 was “generally well-tolerated”. Bill Enright, CEO of Vaccitech, described the data as a “promising step in the right direction”, stating that he looks forward to final data next year”.
“Currently people with persistent HPV infection have no treatment options until they develop high grade lesions.”
Enright referred to repeat cervical screening without a treatment option as a “frustrating and anxiety-provoking” approach.
We look forward to hearing more from Vaccitech at the World Vaccine Congress in Washington. If you would like to join us, get your tickets here.
With just weeks to go until the World Vaccine Congress in Washington this April, we are delighted to share another in our series of exclusive interviews with some of the fantastic speakers lined up for the event. This interview was a zoom conversation with Dr Niranjan Sardesai, founder, President, and CEO of Geneos Therapeutics. Our conversation explored the work that Dr Sardesai and his team and doing in developing personalised cancer vaccines, and how this interacts with research happening in the infectious disease area. A full transcript can be found at the bottom of the page. We hope you enjoy it!
Geneos at a glance
Our first question aims to provide a bit of context to Dr Sardesai’s work and his presence at the Congress. He describes Geneos as a “clinical stage immuno-oncology company” that is developing “exquisitely personalised cancer vaccines” based on its GT-Epic platform and importantly, one that is already seeing dramatic tumour reductions in clinical trials.
How does Geneos approach cancer vaccines?
Dr Sardesai uses the term “exquisitely personalised” in his previous answer, and we were curious about how Geneos is pursuing this goal. For Dr Sardesai, “these are really exciting times for the cancer vaccines field”. Although the understanding of the immune system’s response to tumours is “not a new finding”, the challenge has “always been” encouraging this in more patients.
The approach that Geneos is taking is a “holistic view”. The team wanted to identify the tumour-specific antigens, to develop the right immunity to those antigens, and to understand the “ideal clinical settings”. Thus, the concept of the personalised vaccine, “truly tumour derived from each patient”, was developed. The mutations in tumours are twofold; not only do they enable the cancer to “avoid the immune system”, but they can act as the “Achilles heel of the tumour”, marking the cells to the host immune system.
“So what we’re trying to do is exploit those differences in the cancer cell and because these differences are idiosyncratic, they’re different from each patient to patient. The products that are designed based on these differences necessarily have to be personalised.”
The “core” of the GT-Epic platform is understanding and identifying the unique makeup of each patient’s cancer cell, developing their personalised vaccine, and then treating the patient.
What challenges do these vaccines bring?
From the sounds of it, developing personalised cancer vaccines is not a simple process, so we asked for a bit of a rundown of some of the key challenges that Dr Sardesai and his team encounter. This is a “really fundamental question for the field”, says Dr Sardesai. He suggests that because the technology to identify changes in tumours has been developed through “tremendous improvements in sequencing capabilities”, we are in the “golden age of genomics and bioinformatics”. As such, “external developments” in the wider vaccine space are enabling solutions in the cancer vaccine arena.
“I feel like this is the right time and the right place for cancer vaccines, personalised cancer vaccines, because some of the key technological hurdles around identification have been addressed by the field as a whole. So we’re certainly grateful for that.”
However, for each patient there can be “hundreds of somatic changes”. Consequently, identifying “targetable neoantigens” presents another challenge. Among the community Dr Sardesai identifies “different methods” for identifying these, but for him and his team, the lesson they are taking forward is that “targeting more” of these neoantigens is “going to be preferable”.
“Geneos is taking the approach that we identify all targetable mutations, and we incorporate all of them into our tumour vaccines and let nature make the call.”
Dr Sardesai states that lessons from natural immunity show that the immune system is capable of “driving responses to a large range of immunogens” every day. Thus, the team at Geneos puts the “decision-making process” in the hands of the individual immune system. Another challenge is that “patients and the tumours are certainly not waiting around” for treatments to be developed.
“Speed is of the essence.”
Therefore, a challenge is keeping down the turnaround times from biopsy to treatment. With their DNA-based platform, Dr Sardesai and colleagues have already shrunk this to 6-8 weeks. However, they “know” they can do it in under 4 weeks. This is where a clinical development aspect comes into play, because “sometimes clinical development decisions are made based on the capabilities of the platform”. For example, if a platform has a long turnaround time, it may not be applicable to certain types of cancer or treatment settings.
“What Geneos has done is we’ve shown that we are treating patients with bulky tumours.
So far, results from the field are exciting, showing that personalised cancer vaccines can work in earlier stage cancers to “prevent recurrence.” Perhaps even more dramatic is that Geneos has shown that it can reduce – and even eradicate – bulky tumours and their metastases in patients with advanced cancer. These clinical results have led to the planning of a potentially registrational clinical trial.
Infectious diseases and cancer therapy
For many of our speakers who are not directly engaged in infectious disease research, the field has had implications for their work, whether in terms of COVID-19 disruptions or accelerated technological developments. We asked Dr Sardesai about the interplay between his work and infectious diseases. Interestingly, Dr Sardesai entered the field “from the infectious disease side” and he identifies a “phenomenal impact” on the approach he is taking to cancer vaccines.
A key similarity is the notion of central tolerance. Simply put, years (and years) of evolution have developed an immune system capable of “identifying what is self from foreign”. Although we do experience certain auto-immune diseases, in general, the immune system is fairly confident in making these distinctions. This has been “exploited fundamentally” in infectious disease research, and the cancer field can learn from this by seeing the link between “what is it that drives immunity” and tailoring the immunity to the pathogen.
In cancer, the tumour neoantigens are “non-self”, so Dr Sardesai suggests that “just as we think of viral antigens and bacterial antigens as foreign”, these neoantigens can be perceived as “foreign”. However, for infectious diseases the aim is usually prevention, and in Dr Sardesai’s work the goal is therapy.
As he identifies lessons he has learnt from infectious diseases, Dr Sardesai also hopes to share insights the other way. For example, with recent COVID-19 vaccines, they were “very, very effective” in terms of antibody responses, but “it’s been challenging to do clearance because of lack of T cell immunity”.
“So what we love about the idea is that I think we started out from the infectious disease, we all learnt a lot, what we learnt through developing cancer vaccines is what drives effective cellular immunity, which can then go back into developing better infectious disease vaccines.”
We also like the idea of interaction between the different areas of vaccine development, and this leads us nicely into our final question!
Why the World Vaccine Congress?
We love to understand more from our speakers when it comes to what brings them to the Congress. Dr Sardesai puts it perfectly when he says that it’s been organised to cover “all things vaccines”! This means that “concurrent sessions” will cover every aspect of vaccine development and deployment. In particular, he’s looking forward to the regulatory tracks because “these developments that are going on are happening in real time”.
“I’m looking forward to…being able to interact with colleagues across different silos.”
We really enjoyed this conversation with Dr Sardesai and hope you did too. If you would like to hear more on his work, join us at the World Vaccine Congress this April. To read the full transcript, see below!
In March 2023, RVAC Medicines and the University of Pennsylvania (Penn) announced a collaboration to pursue the development of mRNA vaccines to “modulate the body’s normal immune response as possible treatments” for “certain autoimmune diseases and allergic conditions”. The focus will be on potential vaccines for food allergies and selected autoimmune indications.
Unmet medical needs
A statement from RVAC indicates that autoimmune diseases and allergic reactions or conditions comprise “rising unmet needs” that require “more treatment options” for patients across the globe. Autoimmune diseases occur when the immune system becomes “oversensitive” to harmless proteins and triggers an attack on the body itself.
The US NIH “more than 80 autoimmune diseases”, some of which are well known, and others that are “rare and difficult to diagnose”. Many have “no cure”. RVAC suggests that these diseases have “risen steadily in recent years”. Indeed, an average annual increase of 3% to 9% represents a “growing global health concern”. Allergic reactions or conditions are caused by the immune system being triggered against a “harmless allergen” such as foods or animals.
Addressing these needs
In response to the needs identified above, Dr Drew Weissman of the Perelman School of Medicine at Penn is bringing his team to a collaboration with RVAC to “develop and optimise mRNA vaccine candidates”. The goal is to “induce immune tolerance, thereby reducing the chances of autoimmune responses”.
Dr Weissman describes allergic reactions and “inappropriate autoimmune responses” as “difficult and restrictive” conditions in people’s lives.
“We are excited to begin this collaboration for certain conditions that currently have imperfect and incomplete therapies.”
Dr Sean Fu, CEO of RVAC, is also excited, calling Dr Weissman a “pioneer in the field”.
“With this collaboration, we want to develop mRNA vaccine product candidates with the potential to improve lives of patients who suffer from certain autoimmune diseases and allergies.”
Dr Jason Zhang is RVAC’s Chief Scientific Officer and is “very glad” to work with Dr Weissman for a “broad spectrum” of conditions.
“This collaboration will apply the mRNA technologies to induce antigen-specific immune tolerances, and RVAC is committed to becoming a leader in this field.”
For more detail on the myriad possibilities presented by mRNA approaches, join us at the World Vaccine Congress in Washington this April. Dr Drew Weissman and his lab have been shortlisted for a VIE award at the Congress. To view the lists for each category click here!
Researchers in France published a paper in Nature Communications in March 2023 detailing the results of an investigation into their Lassa fever vaccine candidate. MeV-NP was described in 2021 as providing “sufficient” protection against Lassa fever with just a single dose, between 1 month and 1 year after vaccination.
However, the authors note that due to a “limited dissemination area during outbreaks” and the risks of “nosocomial transmission” it would be useful to develop exposed patients during outbreaks. Thus, in the paper they tested if the “time to protection” could be reduced. Results suggest that although MeV-NP can “induce a rapid protective immune response” against Lassa fever, it “can likely not be used as a therapeutic vaccine”.
The study recognises that Lassa fever, caused by the arenavirus LASV, is a “major public health issue in West Africa” resulting in “thousands of deaths each year”. Unfortunately, “low specificity of early symptoms” means that most cases are confirmed at an “advanced stage”. Thus, there is an “urgent need” for the development of both an effective vaccine and suitable treatments.
In our post on the recent cases in Accra, Ghana, we noted that there are a few collaborations in place to develop vaccine candidates, with WHO ranking Lassa fever in its top priority list of diseases requiring urgent vaccine development. WHO’s target product profile (TPP) for this vaccine demands that it should be safe for all age groups, an ideally confer lasting immunity after a single immunisation.
The authors of the study acknowledge that a “preventative vaccine is preferred over an emergency vaccine” but suggest that the latter would still be “highly valuable” in reducing community or hospital outbreaks.
The vaccine candidate is a recombinant measles virus (MEV) expressing LASV GP and NP of the “prototypic Josiah strain”.
“To improve the immunogenicity of the measles backbone, the vaccine was further engineered to abolish the IFN-antagonist activity of NP.”
Previous research demonstrated that a single shot protected cynomolgus monkeys against the disease, conferring cross-protection against “strains from distant lineages II and VII”, and inducing “long-term immunity”. However, a concern about use in the human population is the “pre-existing immunity against MeV”, which could potentially affect the efficacy of the candidate.
The study explores efficacy, suggesting that the vaccine “fully protects MeV pre-immune cynomolgus monkeys” between 16 to 8 days prior to “lethal infection”.
“This is particularly interesting, as most LASV outbreaks are limited to geographical clusters, for which infected rodents are the amin source of viral dissemination in the human population.”
Thus, a vaccine “capable of rapid protection of an exposed population in an outbreak setting would be highly beneficial”.
The authors note that MeV-NP conferred “comparable protection” in animals that were “naive or pre-immune to MEV”, which supports “no effect of the MeV pre-existing immunity” on its efficacy.
Although this reduced time span is a positive outcome, the vaccine “does not demonstrate therapeutic efficacy in animals vaccinated after challenge”.
“Innate or adaptive immune responses against the MeV vector do not help controlling LASV replication, at least in a therapeutic setup”.
The study shows the efficacy of the vaccine with a “short time to protection” despite this the lack of therapeutic benefit, which offers the possibility of vaccination during an outbreak.
For more on Lassa fever and other disease that particularly affect that African continent, join us for a session with Dr Daniel Bausch at the World Vaccine Congress in Washington next month.
Following positive results from a Phase IIb trial in December 2022, Moderna and Merck have announced that their personalised mRNA cancer vaccine, in combination with KEYTRUDA, has been granted Breakthrough Therapy Designation by the FDA. In a statement in February 2023, the companies stated “excitement” at the “potential promise of individualised cancer treatments”.
A new frontier
As we noted in December, the Phase IIb trial, KEYNOTE-942, produced positive data. The trial enrolled 157 patients with stage III/IV melanoma and compared mRNA-4157/V940 and KEYTRUDA therapy with KEYTRDUA alone for one year.
Dr Stephen Hoge, Moderna’s President, described the trial as “the first demonstration of efficacy for an investigational mRNA cancer treatment”, which “potentially represents a new frontier in treating melanoma and other cancers”.
“We look forward to publishing the full data set and sharing the results at an upcoming oncology medical conference, as well as continuing discussions with health authorities. We are grateful to the FDA for this designation.”
Breakthrough Therapy Designation
The FDA’s Breakthrough Therapy Designation is intended to “expedite the development and review” of candidates for serious conditions where “preliminary clinical evidence indicates that the product may demonstrate substantial improvement over available therapies on at least one clinically significant endpoint”.
Both companies will continue working with regulatory authorities and initiate a Phase III study with a view to expanding to additional tumour types.
Dr Eric H. Rubin, Senior Vice President, Global Clinical Development, Merck Research Laboratories, stated that this was an “important milestone” for the project”.
“We look forward to working with the FDA, in collaboration with Moderna, to conduct a rigorous and rapid clinical development programme with a focus on addressing the needs of this important patient population”.
For more from Moderna and Merck and specific tracks devoted to cancer vaccine development, join us at the World Vaccine Congress in Washington this April.
In February 2023 Scancell announced completion of a monotherapy dose finding arm of the Phase I/II ModiFY clinical trial. Data demonstrated that the Modi-1 cancer vaccine was “safe and well tolerated” with “encouraging early efficacy” in a head and neck cancer patient.
Modi-1 in trial
Modi-1 is the first candidate from Scancell’s Moditope platform and targets four different types of cancer: HGSOC, TNBC, head and neck squamous cell carcinoma (SCCHN) and renal cell carcinoma (RCC). The Modi-1 peptides are linked to AMPLIVANT, an adjuvant from ISA Pharmaceuticals.
Modi-1 is intended to stimulate CD4 T cells, which may “directly impact tumour growth”. For some patients, however, these T cells “may need to be protected by CPIs if the tumour environment is highly immunosuppressive”.
The ModiFY trial is an “open-label, multicohort, multicentre, adaptive” trial of Modi-1 in patients with “unresectable HGSOC, SCCHN, TNBC, or RCC”. Patients are treated with Modi-1 or Modi-1 and a CPI. Scancell reports that a total of 23 patients have been vaccinated, with 55 doses administered. All had “skin reactions” at the site of injection “consistent with a delayed-type hypersensitivity (DTH) reaction”. This indicates a T cell response.
The first study cohort confirmed the safety profile and the objective for Cohort 2 was to “assess the safety of the two citrullinated vimentin peptides plus an enolase peptide at a higher dose”. Following safety data from the second cohort, the trial was expanded for Modi-1 monotherapy in all four tumour types.
Dr David Pinato, Principal Investigator at Imperial College, described advanced ovarian cancer as “aggressive” and “hard to treat”.
“The early efficacy data showing that the Modi-1 vaccine is stabilising this advanced disease is very encouraging.”
Professor Christian Ottensmeier, Chief Investigator at the University of Liverpool, believes that “this therapeutic cancer vaccine could have significant potential”.
“Further studies with Modi-1 monotherapy and in combination with CPIs should tell us in which settings it will have maximum benefit to patients.”
Professor Lindy Durrant, CEO at Scancell, is “highly encouraged with the early efficacy data”.
“These results allow us to proceed with the monotherapy expansion cohorts and into the cohorts in combination with checkpoint inhibitors as planned.”
For more on cancer therapy and different vaccination approaches at the World Vaccine Congress in Washington this April get your tickets today.
In February 2023 Gritstone bio and the National Cancer Institute (NCI) of NIH announced a collaboration to evaluate an “autologous T cell therapy expressing a T cell receptor targeting mutated KRAS in combination with Gritstone’s KRAS-directed vaccine candidate”. The Phase I study will be led by Dr Steven A Rosenberg of the NCI’s Centre for Cancer Research.
The vaccine candidate, SLATE-KRAS, is an “off the shelf” neoantigen vaccine that “demonstrated early evidence of efficacy” in an ongoing study. Based on these results, Gritstone is initiating a separate, randomised study evaluating SLATE against a KRAS mutation driven tumour type.
Through this agreement, NCI will identify patients with metastatic cancer who are eligible for adoptive cell transfer “based on the presence of a G12V or G12D KRAS mutation”. Gritstone will provide the vaccine for the trial.
Dr Andrew Allen, Co-founder, President, and CEO of Gritstone bio is “privileged to establish this collaboration”.
“To date, cell therapy’s success in treating blood cancers has not translated to the more common solid tumours. There is a mechanistic synergy in having cell therapy and cancer vaccines in combination.”
Dr Allen is “thrilled” to test the programme in patients and looks forward to a “promising study”.
A rational approach
Dr Karin Jooss, Executive Vice President and Head of R&D at Gritstone bio described the “use of neoantigen vaccines to enhance the potency of neoantigen-directed T cell therapy” as an “attractive concept”. The KRAS-directed vaccine has a demonstrated ability to ‘induce and expand KRAS mutation-specific T cells” and “drive them into solid tumours”.
“Combining this modality with autologous KRAS mutation-specific TCR transduced T cells…is a rational approach to augmenting therapeutic efficacy”.
We look forward to hearing more on efforts towards cancer vaccines from Dr Andrew Allen at the World Vaccine Congress this April. To join us there get your tickets today.
In February 2023 VBI Vaccines announced interim data from a Phase II study evaluating a combination treatment of VBI-2601 (BRII-179) and BRII-835 (VIR-2218) in chronically infected HBV patients. The data demonstrates that the therapy was “generally well-tolerated”. It also “restored strong anti-HBsAg antibody responses and led to improved HBsAg-specific T-cell responses, when compared to BRII-835 alone”.
VBI-2601 is a “novel recombinant, protein-based HBV immunotherapeutic candidate”. VBI states that it “builds upon the 3-antigen conformation of VBI’s prophylactic 3-antigen HBV vaccine candidate” and is intended to treat enhanced B-cell and T-cell immunity.
The Phase II study is a randomised, multi-centre trial across sites in Australia, Taiwan, Hong Kong, South Korea, New Zealand, Singapore, and Thailand. It is sponsored by VBI’s partner Brii Biosciences.
Interim data were generated from 50 adult, non-cirrhotic patients who received “nucleos(t)ide reverse transcriptase inhibitor (NRTI) therapy” for at least 12 months. They were randomised and dosed across three cohorts:
BRII-835 Alone Regimen – Nine subcutaneous 100mg doses of BRII-835, dosed every four (4) weeks through Week 32
BRII-835 Alone Regimen + nine 40µg intramuscular doses of VBI-2601 admixed with interferon-alpha (IFN-α) as co-adjuvant every four weeks from Week 8 through Week 40
BRII-835 Alone Regimen + nine 40µg intramuscular doses of VBI-2601 without IFN-α every four weeks from Week 8 through Week 40
Dr Francisco Diaz-Mitoma, VBI’s Chief Medical Officer, stated that “numerous studies” have already assessed the potential of siRNA candidates in HBV patients, but this is the “first time we’ve seen data from the combination of an HBV siRNA with an HBV-specific immunomodulator”.
“We are very encouraged by these interim data, which suggest that the combination…has the potential to be a meaningful part of a functional cure regimen.”
Further data are expected “later this year”. For more on the challenges associated with the development of HBV therapies, read our interview with Dr Andrew Vaillant here.
We will hear more about HBV approaches at the World Vaccine Congress in Washington this April. Join us there by getting your tickets now!
In research published in Nature biomedical engineering a team of scientists at Northwestern University’s International Institute for Nanotechnology (IIN) explored the effects of structural changes to cancer vaccines. Using chemistry and nanotechnology they changed the location of adjuvants and antigens on and within a nanoscale vaccine with positive consequences.
The team used spherical nucleic acid (SNA) nanoparticles to “investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production, and the induction of memory”. Their conclusion is that “the structural design of multi-antigen vaccines substantially impacts their efficacy”.
Current vaccine approaches
News Medical describes the “conventional” vaccine approach as a blend of antigen and adjuvant, which is then injected into the patient. As there is “no control over the vaccine structure” there is “limited control over the trafficking and processing of the vaccine components”. Thus, we can’t control the efficacy of the vaccine.
Dr Michelle Teplensky, one of the study authors, suggests that a “challenge” associated with this “blended mish mosh” approach is that “an immune cell might pick up 50 antigens and 1 adjuvant or 1 antigen and 50 adjuvants”. However, there “must be an optimum ratio of each that would maximise the vaccine’s effectiveness”.
The study indicates that “increasing efforts have been made to develop vaccines targeting identified tumour-associated proteins”. However, although there are “some benefits” to these, “many are designed to primarily activate cytotoxic T cells”.
“Tumour can have considerable heterogeneity and high mutational burdens that allow for easy escape of immune surveillance.”
With cytotoxic T cell activity reliance, current vaccines are “inadequate” and necessitate “vaccines containing antigens targeting multiple immune cell types to induce enhance tumour remission”. Dr Teplensky emphasises that the “more types of cells the immune system has to go after tumours, the better”.
What are they changing?
SNAs, a structural platform developed by Professor Chad Mirkin, Director of the IIN, enable scientists to identify the specific quantities of antigens and adjuvants being delivered to cells, as well as how they are being presented and processed. This novel approach, “rational vaccinology” as Professor Mirkin calls it, recognises that the structural presentation of a vaccine is just as important as its contents.
Professor Mirkin suggests that rational vaccinology allows vaccines to “deliver the precise dose of antigen and adjuvant to every immune cell” so that they are “all equally primed to attack cancer cells”.
“If your immune cells are soldiers, a traditional vaccine leaves some unarmed; our vaccine arms them all with a powerful weapon with which to kill cancer.”
In the study, the authors explore the “vaccine-design space involving multiple cell-targeting antigens.” The vaccines they investigated respond to specific structural placements of antigen targets to “prime the immune system most effectively”. The most potent approach for a cancer vaccine structure in this work involved attaching two different antigens to an SNA comprising a shell of adjuvant. This resulted in a 30% increase in antigen-specific T cell activation. In several animal models the nanostructures stalled tumour growth.
What will this mean for the future?
The authors state that the power to “optimise antigen presentation” to meet the “desired signalling profile” will be “critical” to the future of powerful vaccines. They hope that the developments in their study will offer a “path forward to rethink the design of vaccines for cancer and other diseases”.
With “remarkable” data, they produced a potent vaccine with the same compositional features as a less effective vaccine. However, their success may not be limited to cancer. Another possible advantage to rational vaccinology is the ability to change the vaccine to apply to a different disease. Dr Teplensky hopes that their work affords potential for “almost any type of cancer” and “vaccines across the board”.
We look forward to hearing more updates on cancer vaccine progress at the World Vaccine Congress in Washington later this year, and more positive stories from our vaccine community in the meantime.
Swiss based AC Immune reported in January 2023 that ACI-24.060, its anti-amyloid-beta (Abeta) vaccine, had “elicited an anti-Abeta antibody response” and was “well tolerated” in patients with prodromal Alzheimer’s disease (AD). It will therefore move to a second cohort in the ABATE trial.
The trial is a Phase Ib/II multicentre, adaptive, double-blind, randomised, placebo-controlled study to assess the “safety, tolerability, immunogenicity, and pharmacodynamic effects” of the vaccine candidate ACI-24.060 in subjects “with prodromal Alzheimer’s disease and in adults with Down syndrome”. Participants were required to have brain Abeta pathology confirmed by a positron emission tomography (PET) scan.
The trial will now be “expanded, as planned” to include individuals with Down syndrome and to “evaluate higher doses in Alzheimer’s patients”. Early results showed that a low dose of the vaccine could elicit an anti-Abeta antibody response “as soon as week 6”, which is 2 weeks after the second injection.
ACI-24.060 is “derived from AC Immune’s SupraAntigen platform” and has already demonstrated an ability to “induce a strong polyclonal antibody response that matures and is maintained against both oligomeric and pyroglutamate-Abeta species”. These are “key pathological forms of Abeta”, associated with Abeta plaque formation and disease progression.
The vaccine is designed to “enhance the formation of broad-spectrum protective antibodies” with the “same safety and tolerability previously demonstrated” in the ACI-24 programme.
“This investigational candidate has the potential to efficiently inhibit plaque formation and increase plaque clearance, and thereby may reduce or prevent disease progression.”
An approved approach
AC Immune states that “targeting Abeta using antibodies has recently been validated with FDA approvals of new monoclonal antibody treatments for patients with AD”. The vaccine programme is intended to “ultimately deliver significant benefits to patients, their caregivers, and healthcare systems”. With “safety and tolerability” meeting “low frequency dosing, low overall costs, and durable responses” it is hoped that this could become a reality.
Dr Andrea Pfeifer, CEO of AC Immune SA is “delighted with the encouraging initial safety and immunogenicity findings”.
“We believe ACI-24.060’s successful development could provide patients with a novel therapeutic option offering numerous potential advantages in treatment, maintenance, and prevention settings.”
Dr Johannes Streffer, CMO of AC Immune SA, suggested that the “innovative” design of the study with provide an opportunity for “early de-risking”.
“Moreover, the inclusion of cohorts of participants with DS in the trial positions us to potentially address the needs of a vastly underserved vulnerable population, virtually all of whom will develop amyloid plaques and AD.”
He thanked trial participants and investigators for their continued efforts.
For more on vaccines against dementia read our previous post here. To learn more about potential vaccine therapies and technologies and the World Vaccine Congress in Washington get your tickets now.
In January 2023 LinKinVax and Gustave Roussy announced a collaboration towards a first-in-human Phase I/IIa clinical trial on a therapeutic vaccine candidate. This vaccine, CD40HVac, will target head and neck cancer associated with human papillomavirus (HPV). The study aims to demonstrate the safety and immunogenicity of the vaccine and determine the recommended Phase II dose.
LinKinVax is a clinical-stage biotechnology company that specialises in protein-based vaccines. It suggests that it hopes to “disrupt vaccine development using a unique dendritic cell-targeting vaccine platform”.
The vaccine platform is reportedly constructed around a humanised monoclonal antibody, which is “fused with regions of pathogens of interest” to target the CD40 molecule expressed by dendritic cells (DC). This strategy is useful because a “small quantity of antigens” is required to activate the immune system with the effect of lasting responses.
Gustave Roussy was ranked the 3rd best oncology hospital in the world according to Newsweek and treats patients of all ages with all types of cancer.
“We place innovation at the heart of a human, scientific, and technological revolution in the fight against cancer.”
Caring for almost 50,000 patients every year, the centre combines research with patient care and teaching. It specialises in the treatment of rare and complex cancers.
The study will investigate the safety and immunogenicity of the CD40HVac candidate with the Poly-ICLC adjuvant against “oncogenic HPV in patients with head and neck cancer”. Further exploratory objectives are planned to “estimate progression-free survival and overall survival”.
CD40HVac is a therapeutic vaccine for “HPV-associated malignancies”. CDC research has indicated that 62% of oropharyngeal cancers are attributable to HPV 16 and 18. Despite the power of “modern multidisciplinary treatment approaches” against HPV-induced tumours, the collaboration is needed to “better address the needs of patients”.
Professor Yves Levy, Chief Medical and Scientific Officer at LinKinVax, described the partnership as a “crucial step”.
“It represents a bridge between basic research and clinical research designed to accelerate innovation for the benefit of patients.”
Dr Carline Even from the Department of Head and Neck Oncology at Gustave Roussy commented on the importance of “innovation” in the “fight against cancer”.
“We hope that this first project will be inaugural of a long-standing and synergistic collaboration between LinKinVax and Gustave Roussy.”
In January 2023 BioNTech announced that it had signed a Memorandum of Understanding (MoU) with the UK government to “benefit patients”. The goal will be to accelerate clinical trials for personalised mRNA therapeutics with a target of providing personalised cancer therapies for “up to 10,000 patients by the end of 2030”.
A statement from BioNTech describes the objective as a component of a “multi-year collaboration focused on three strategic pillars: cancer immunotherapies based on mRNA or other drug classes, infectious disease vaccines, and investments into expanding BioNTech’s footprint in the UK”.
Under the MoU trial site development and patient recruitment for clinical candidates will accelerate. Using the UK’s clinical trial network, genomics, and health data assets, they hope to move faster along BioNTech’s pipeline. Following this acceleration, the collaboration will select candidates, trial sites, and set up a development plan. The aim is to be “ready to enrol the first cancer patient in the second half of 2023”.
The plans involve BioNTech’s investment in an R&D “hub” in Cambridge, with an “expected capacity of more than 70 highly skilled scientists”. It will also establish a regional headquarters in London. Furthermore, the company will “remain the local sponsor of current and upcoming new clinical trials of its programmes in the UK and will design the clinical trial protocols”.
What does this mean for patients?
The government statement suggests that cancer patients will get “early access” to trials for personalised therapies such as cancer vaccines. Access will be through the Cancer Vaccine Launch Pad, which is being developed by NHS England and Genomics England. The launch pad is intended to “rapidly identify large numbers of cancer patients who could be eligible”.
From COVID-19 to cancer
Professor Ugur Sahin is CEO and Co-Founder of BioNTech recognised the collaboration between the UK’s NHS, academia, regulatory bodies, and the private sector during the COVID-19 pandemic as “exemplary”.
“This agreement is a result of the lessons learnt from the COVID-19 pandemic as we all experience that drug development can be accelerated without cutting corners if everyone works seamlessly together towards the same goal. Today’s agreement shows that we are committed to do the same for cancer patients.”
BioNTech has been working on the relevant technologies for “over 20 years”. The collaboration will therefore accelerate better outcomes for patients in the UK and worldwide. Health and Social Care Secretary Steve Barclay emphasised the importance of ensuring the “best possible treatments are available as soon as possible” for cancer.
“BioNTech helped lead the world on a COVID-19 vaccine and they share our commitment to scientific advancement.”
Cancer research under pressure
Although Cancer Research UK “welcomed” the news, the charity stated concern over delays in diagnosis and treatment. Staff are coming under increasing pressure and may struggle to facilitate clinical trials. CRUK spokesperson Dr Iain Foulkes suggested that “mRNA vaccines are one of the most exciting research developments to come out of the pandemic, and there are strong hints that they could become powerful treatment options for cancer”.
“Getting there will require lots more research.”
For more on cancer vaccine development at the World Vaccine Congress in Washington 2023 get your tickets today.
In findings from Brigham and Women’s Hospital published in Science Translational Medicine in January 2023, researchers reveal newly discovered potential to exploit cancer cells in the fight against cancer. Using a “dual-action, cancer-killing vaccine” in an advanced mouse model of glioblastoma, they report “promising results”. This means not only tackling established tumours but seemingly inducing long-term immunity by training the immune system to prevent further cancer. As we explored in a previous post on glioblastoma therapy, glioblastoma is a “complex” and aggressive cancer.
A simple idea
Dr Khalid Shah, director of the Centre for Stem Cell and Translational Immunotherapy (CSTI) and vice chair of research at the Department of Neurosurgery at the Brigham, suggests that the team has “pursued a simple idea”. The intention was to “take cancer cells and transform them into cancer killers and vaccines”.
“Using gene engineering, we are repurposing cancer cells to develop a therapeutic that kills tumour cells and stimulates the immune system to both destroy primary tumours and prevent cancer.”
Although the study focuses on glioblastoma, the overall strategy is believed to be applicable to a wider range of tumours. Dr Shah emphasised that despite the “highly technical” nature of the team’s work, “we never lose sight of the patient”.
“Our goal is to take in innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that ultimately will have a lasting impact in medicine.”
A novel approach
Although many labs are pursuing cancer vaccines, the Brigham suggests that Shah and his colleagues have taken a “distinct” approach. Rather than using inactivated tumour cells, they repurposed living tumour cells.
“Like homing pigeons returning to roost, living tumour cells will travel long distances across the brain to return to the site of their fellow tumour cells.”
Thus, when transformed into “cell killing” agents, they will actively return to the tumour site to wreak havoc. The study describes how the researchers “repurposed the tumour cells from interferon-β (IFN-β) sensitive to resistant using CRIPR-Cas9″. This is a unique gene editing tool that allowed the team to engineer the cells to “release immunomodulatory agents IFN-β and granulocyte-macrophage colony-stimulating factor”.
When tested in mice these therapeutic tumour cells (ThTCs) “eliminated established glioblastoma tumours” by “inducing capase-mediated cancer cell apoptosis, down-regulating cancer-associated fibroblast-expressed platelet-derived growth factor receptor β, and activating antitumour immune cell trafficking and antigen-specific T cell activation signalling”.
Putting the cells to the test
These ThTCs were tested in different mice strains. The team also built a safety switch into the cells, which, when activated, could eradicate them if needed. Brigham describes the therapy as “safe, applicable, and efficacious” in the models.
“While further testing and development is needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.”
This step in the development of a potential therapy is exciting; Brigham calls for further investigations and we look forward to learning more about the possibilities they will hold.
At the World Vaccine Congress in Washington in April we have specific tracks dedicated to the discussion of cancer vaccines, and we anticipate great interest in these debates. To join us, get your tickets today.
Towards the end of 2022 we noted the positive results of a Moderna/Merck trial for a personalised cancer vaccine in combination with KEYTRUDA therapy. After the mRNA momentum of the pandemic, there appears to be a sense of optimism in the therapeutic community for the power of this technology to make a difference to a range of treatments. So, what progress can we expect to see this year, and who will be driving it?
The announcement of the recent successful collaboration between Moderna and Merck resulted in significant financial interest, as noted by the Financial Times: “the 27 per cent – or $16.8bn – jump in Moderna’s market value over two days following the announcement reflected investors’ wider hopes for cancer vaccines”. As the commentary suggests, the influx of investment and understanding during the pandemic has left companies like Moderna and BioNTech in a strong position to make waves on the therapeutic scene. As we go forward into further trials, hopes are high.
The founders of BioNTech have encouraged this hope through suggestions that recent breakthroughs were driving their progress towards therapies. They are targeting a range of cancers with mRNA technology.
Friend or foe?
After its success in the COVID-19 vaccines, it would be natural to expect that mRNA would be a firm favourite for the future of vaccines. However, fears about the effect that it has on the body have taken hold and bee exploited by anti-vaccine populations. The unfounded claim that it might be able to “alter” a person’s DNA is particularly worrying. Dr Paul Offit, Director of the Vaccine Education Centre, explained in 2021 that there are 3 key reasons why this is “not possible”.
“the fact that the mRNA can’t enter the nucleus; the fact that the mRNA isn’t DNA and would need to be translated or reverse transcribed back to DNA; and because it can’t be integrated into DNA, it is not possible for messenger RNA to alter DNA”.
Despite this assurance, fears continue to spread, particularly on social media, and this has the potential to undermine research efforts into therapeutic possibilities. Hopefully, with renewed investment and continued education, this will change. If mRNA truly is the “blueprint” that Professor Ozlem Tureci suggests it is, 2023 promises to be an exciting year for therapies.
For much more on cancer therapies at the World Vaccine Congress in Washington 2023, get your tickets now.
In December 2022 Moderna and Merck announced positive results from a Phase IIb trial of mRNA-4157/v940, an investigational personalised cancer vaccine, in combination with Merck’s anti-PD-1 therapy KEYTRUDA. In this trial, the combination approach demonstrated a “statistically significant and clinically meaningful improvement” in the primary endpoint of “recurrence-free survival (RFS)” compared to KEYTRUDA alone for the treatment of patients with stage III/IV melanoma following complete resection.
mRNA makes waves
As we explored in October 2022, mRNA progress against cancer is hotly anticipated after its success in COVID-19 vaccination strategies. This candidate, mRNA-4157/V940, is a novel personalised cancer vaccine comprising a “single synthetic mRNA coding for up to 34 neoantigens”. This is designed and developed from the “unique mutational signature of the DNA sequence of the patient’s tumour”.
“Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.”
The process and the trial
Stéphane Bancel, CEO of Moderna, published a blog post in which he described the process behind developing personalised cancer vaccines. He stated that study participants have blood drawn and tumours biopsied before lab sequencing. This presents a comparison between the biopsy sample and healthy blood cells, to “identify the unique genetic mutations” of that person’s cancer.
The next stage involves a “proprietary algorithm developed in collaboration with Merck”, which reviews the mutations and predicts up to 34 that are suspected to help the immune system recognise and “attack” tumour cells.
“Next, the investigational personalised mRNA cancer vaccine is created to give cells instructions to make the ‘fingerprint’ cancer protein”.
The vaccine is then manufactured and shipped to the trial site. Patients were injected with their vaccines in order to investigate the effects of combination treatment with KEYTRUDA, compared to KEYTRUDA alone. KEYTRUDA is “considered a standard of care in adjuvant melanoma”. The results were positive: “adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44%”.
Good for the field
Mr Bancel stated that the results are “highly encouraging for the field of cancer treatment”. He indicated that the next steps involve “additional studies in melanoma and other forms of cancer”. The goal is to bring “truly individualised cancer treatments to patients”.
Dr Dean Y. Li is President of Merck Research Laboratories and described the “positive findings” as an “important milestone in our collaboration with Moderna”. The joint statement from the companies looks forward to discussing the results with regulatory authorities and the initiation of a Phase III study melanoma patients in 2023.
To hear more from both Moderna and Merck at the World Vaccine Congress in Washington next year, get your tickets today.
As we gear up towards the World Vaccine and Immunotherapy Congress in San Diego later this month we have been meeting a few of our speakers to get some exclusive insights before their sessions. Dr Stephen Johnston will be representing Calviri Inc. as founding CEO. With almost 200 peer-reviewed papers and 45 patents, as well as teaching positions, his time is precious, so we were very lucky to secure a moment for a zoom interview.
Introducing Dr Johnston
Dr Johnston kindly gave us an overview of Calviri’s work, developing vaccines and diagnostics for cancer.
What can we expect at the Congress?
Although we want to save the best for the Congress, we asked Dr Johnston for a quick preview of some of the content. He explained that he will be trying to encourage his colleagues to accept a “different perspective” on cancer vaccines. He believes they can be “simpler”, less “complicated”, and “less expensive”.
What changes does Calviri Inc. hope to bring to the field?
Anyone who might be familiar with Calviri’s website will know that “outdated” isn’t the strongest term used to describe current approaches to cancer. Dr Johnston acknowledges that this might be a bit “incendiary” but suggests that it’s how he sees it. With “50 years” and “2 Moon Shots“, there “isn’t much to show” for the hard work that has been done. Furthermore, the progress that has been made is inaccessible to people who need it most.
“People sometimes forget that of the 10 million cancer deaths a year, about 7 million of those occur in the developing countries”.
For Dr Johnston and his team, the first key strategy is “early detection”, which leads to higher cure and longer survival rates. Next, they hope to pair this with a “simple, safe, systemic” treatment – a vaccine in their case. Targeting the major cancers, they are creating off-the-shelf solutions.
In a lot of our previous posts we have explored some of the challenges associated with cancer vaccine development. For Dr Johnston, the main issue is targeting key “components” in the make-up of the cancer. He suggests that until now the “community thought that that wasn’t possible” because they were looking at DNA, instead of RNA. Thus, Calviri’s new approach takes on the RNA components that are shared across patients and even tumour types.
How do you keep people motivated?
Our next question reflects the longevity of cancer and the difficulty we have had in developing therapies and preventative measures so far. Dr Johnston suggests that instead of accepting the idea that it is impossible, his team are investigating whether their technology can be applied to cancer prevention.
“Could you design a vaccine to give to people, so that they don’t get it in the first place?”
They have shown in a study in 800 dogs that it is possible to prevent cancer, and so they hope to take this to the next stage in human prevention. The trial in dogs was the “largest” trial in dogs that has ever run, and Dr Johnston believes that after this challenge, humans are “probably easier”.
Accessibility in mind
Dr Johnston mentioned earlier in the interview that accessibility has a huge influence on his work. When we asked more about this, he stated that the team had set goals to meet in terms of production costs, in order to keep the vaccine affordable. They are “quite confident” that this can be done; Dr Johnston emphasises this by suggesting that if dogs can be easily vaccinated then the vaccine can be administered in developing areas. Not only that, but he expects it do be done “profitably”.
Looking forward to the Congress
Our final question gets to the bottom of Dr Johnston’s attendance at the Congress later this month, apart from the importance of sharing his work with others! He explained that he is “open” to hearing from people with platforms that he and his team could use. Having spoken to a few colleagues already, he is looking forward to meeting in person to further the conversation. Finally, he is testing the waters of the cancer community. Previously it has been “rutted” and “stovepiped” so this will be an opportunity to see how imaginative people are prepared to be in the future!
We are grateful for Dr Johnston’s time, particularly so close to the Thanksgiving holiday. If you are curious about his work and want to learn more at the Congress, get your tickets now.
In November 2022 the results of the AELIX-002 trial were published in Nature by collaborators from Aelix Therapeutics and Gilead Sciences. This is the trial that Dr Christian Brander, Co-founder and Chief Scientific Officer at Aelix Therapeutics, hinted at in our exclusive interview during the World Vaccine Congress in Barcelona 2022. Dr Brander is reportedly “excited” to have his team’s results recorded in a “prestigious journal” with a global reach.
The trial in context
The WHO reported that in 2021 38.4 million people were living with HIV. WHO’s strategy for 2022-2030 aims to “reduce HIV infections from 1.5 million in 2020 to 335,000 by 2030”. UNAIDS reports that 28.7 million people were accessing antiretroviral therapy in 2021.
The authors of the study note that therapeutic vaccines targeted to HIV-specific immunity have been “postulated to be a key component of any HIV cure strategy”. Despite the safety and immunogenicity of different candidates in trials, “no reduction in HIV-1 viral reservoirs, prevention of viral rebound, or suppressed viremia off ART have been reported” in trials such as this one.
A “potential reason” for previous “suboptimal trials outcomes” might be “T-cell immunogen designs and the induction of virus-specific T-cell responses with ineffective or insufficient antiviral activity”. In order to overcome this issue, HTI (HIVACAT T-cell immunogen)-based vaccines were designed to “induce functional HIV-1-specific T-cell responses that were associated with better viral control”.
The trial meets endpoints
The trial was a “double-blind, randomised, placebo-controlled trial” with the primary objective of safety evaluation. The secondary objectives “included T-cell immunogenicity, the effect on viral rebound, and the safety of an antiretroviral treatment interruption” (ATI). The study “demonstrated that HTI vaccines were safe, well-tolerated, and able to induce strong, polyfunctional, and broad CD4 and CD8 T-cell responses focused on the HTI immunogen sequence”.
“The AELIX-002 trial results support the idea that the induction of HIV-specific T-cells is a key factor in improving post-rebound viral suppression during an ATI, while validating the design of the HTI immunogen to induce functional T-cell responses to vulnerable sites of the virus”.
The authors believe that their findings “strongly support” the further use of HTI vaccines in “simpler regimens, given alone, or in combination”. A second study is also being conducted in collaboration with Gilead, according to Pipelinereview.com. Dr Brander remarked that the “T-cell vaccine approach has the potential to play a critical role in strategies to cure HIV infection”.
“AELIX is a leader in developing vaccine-based solutions for an HIV cure.”
For more on HIV strategies at the World Vaccine and Immunotherapy Congress get your tickets now.