by Charlotte Kilpatrick | Sep 4, 2024 | Technology |
3PBIOVIAN announced in September 2024 that it has been selected by Rokote Laboratories Finland Ltd. as CDMO partner for GMP manufacturing of adenovirus type 5 (Ad5) vector-based candidate expressing a modified SARS-CoV-2 spike protein. The partnership aims to bring Rokote Laboratories’ intranasal FINCoVac 2.1 vaccine to Phase I clinical studies with 3PBIOVIAN providing Drug Substance and Drug Product. FINCoVac 2.1 is intended to elicit a strong mucosal immune response in the nasopharyngeal cells, potentially preventing infection and transmission.
Ad5 vector
The agreement covers GMP manufacturing of the Ad5 vector using 3PBIOVIAN’s standard process at facilities in Turku, Finland. With “extensive experience” in adenovirus GMP manufacturing solutions, 3PBIOVIAN pursues “successful scalability and GMP compliance”. To meet Rokote Laboratories’ “urgent” needs, the programme has advanced “exceptionally fast”.
FINCoVac 2.1
Rokote Laboratories seeks to “consolidate” the use of new vaccine technology in Finland, focusing on a second-generation coronavirus vaccine, FINCoVac 2.1. It is designed to “meet the challenge of the rapidly mutating variants” with applications as an “easy-to-dose booster”. The vaccine consists of an adenoviral vector, to which the SARS-CoV-2 viral spike protein gene has been transferred. FINCoVac is administered intranasally, so it is expected to offer a “wider immune response” than vaccines that are administered intramuscularly.
Dr Erkko Ylösmäki, CEO of Rokote Laboratories, is pleased with the partnership with 3PBIOVIAN to manufacture the vaccine.
“The ability to use 3PBIOVIAN’s standard process for rapid GMP batch production, along with their extensive experience with adenovirus-based processes, made 3PBIOVIAN the ideal CDMO partner.”
Dr Ylösmäki is excited to start the collaboration and hopes that “together we can further advance Finnish vaccine development”. Deputy CEO at 3PBIOVIAN, Antti Nieminen, commented that the company has “about two-decade-long history” in viral vector development processes and GMP-manufacturing of adenoviruses.
“We are happy to have a role in the journey of this novel second-generation coronavirus vaccine to clinical trials.”
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by Charlotte Kilpatrick | Aug 6, 2024 | Therapeutic |
ImmunityBio announced in August 2024 that a clinical trial to study ANKTIVA and the investigational AdHER2DC vaccine in individuals with HER2-expressing endometrial cancer has opened. The trial is sponsored by the US National Cancer Institute (NCI) and seeks to assess the safety and preliminary clinical efficacy of the AdHER2DC vaccine in combination with ANKVITA, pembrolizumab, and lenvatinib before a larger study. Endometrial cancer is the most common gynaecological cancer in the US, affecting more than 65,000 women every year. The 5-year overall survival rate in patients with metastasis is “around 20%”, and treatment options after the second-line treatment are “limited”.
ANKTIVA and AdHER2DC
ANKTIVA is ImmunityBio’s IL-15 superagonist immune enhancer; it was approved by the FDA for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumours in April 2024. The AdHER2DC vaccine targets the HER2 protein, which is elevated in 30% of patients with endometrial cancer and in more than 50% of “high-risk subtypes”. The autologous vaccine uses participants’ blood cells that are drawn through apheresis.
The vaccine, a dendritic cell vaccine that is “transduced with an adenoviral vector expressing extracellular domain and transmembrane domain of HER2”, proved to be “well tolerated” and demonstrated “preliminary clinical benefit” in 21 evaluable patients. In this trial, all participants will receive the vaccine and the FDA-approved drugs (pembrolizumab and lenvatinib), and some will receive ANKTIVA.
The study
The Phase I/II study is an open-label, two-arm study; the first phase will determine the recommended dose of each intervention in participants with HER2 positive endometrial cancer. The Phase II section will assess the efficacy of the combination in qualified participants. The study will enrol 60 subjects and is scheduled to complete in 2026. Dr Patrick Soon-Shiong, Executive Chair and Global Scientific and Medical Officer at ImmunityBio, is “pleased to partner with the NCI” on the “important” study.
“We are hopeful that the AdHER2DC investigational vaccine plus ANKTIVA will ‘rescue’ the checkpoint inhibitor pembrolizumab and kinase inhibitor lenvatinib and lead to an improved response compared with the current standard of care in this high-risk population.”
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by Charlotte Kilpatrick | Jul 31, 2024 | Global Health |
A paper in Nature Communications in July 2024 explores the effect of COVID-19 vaccines on cardiovascular diseases by examining longitudinal health records from 45.7 million adults in England between December 2020 and January 2022. The authors find that the incidence of common arterial thrombotic events and the incidence of common venous thrombotic events were lower after vaccination. However, there was a higher incidence of previously reported “rare harms” after vaccination. Overall, the researchers offer their findings in support of “wide uptake of future COVID-19 vaccination programmes”.
The study
Although SARS-CoV-2 vaccination “prevented 14.4 million deaths from COVID-19″ across the world in the first year of the pandemic, the authors identify a need to understand the risk of thrombotic and cardiovascular complications. COVID-19 vaccines are associated with rare cardiovascular complications:
- mRNA-based brands are associated with myocarditis
- Adenovirus-based brands are associated with vaccine-induced thrombotic thrombocytopenia (VITT)
In their study, the authors use whole population longitudinal electronic health records for 45.7 million adults in England to quantify associations of first, second, and booster doses of mRNA and non-mRNA COVID-19 vaccine brands with subsequent thrombotic and cardiovascular events. Through Cox regression, they estimated adjusted hazard ratios (aHRs) and corresponding 95% confidence intervals in time intervals since vaccination, adjusted for various co-morbidities, age, sex, and prior COVID-19.
“We show that the incidence of thrombotic and cardiovascular complications was generally lower after each dose of each vaccine brand, except for previously recognised rare complications of the ChAdOx1 vaccine and the mRNA vaccines.”
Findings and implications
Although the incidence of thrombotic and cardiovascular complications was “generally lower” after each dose of each vaccine brand, the authors highlight exceptions. These are consistent with previous findings:
- ChAdOx1 vaccine (ICVT and thrombocytopenia)
- mRNA vaccines (myocarditis and pericarditis)
“These findings, in conjunction with the long-term higher risk of severe cardiovascular and other complications associated with COVID-19, offer compelling evidence supporting the net cardiovascular benefit of COVID vaccination.”
Some of the key findings include:
- The incidence of composite arterial thrombotic events (AMI, ischaemic stroke, and other arterial embolism) was similar or lower after first, second, and booster doses of ChAdOx1 and BNT-162b2 vaccines and booster doses of mRNA-1273, compared to follow-up before or without the corresponding dose.
- The incidence of composite venous thrombotic events (PE, DVT, ICVT, PVT) was generally lower after first, second, and booster doses vaccination, compared to follow-up before or without the corresponding vaccine dose.
- Myocarditis incidence was higher after first dose of BNT-162b2 vaccine, higher one week after second dose of BNT-162b2, and higher after some mRNA booster vaccinations.
- Pericarditis incidence was higher after the first dose of ChAdOx1, after first dose of BNT-162b2, after second dose of BNT-162b2, and after mRNA-based booster vaccination.
The paper offers “reassurance” on the cardiovascular safety of COVID-19 vaccines, finding lower incidence of common cardiovascular events that outweighs the higher incidence of their known rare cardiovascular complications. Additionally, no novel cardiovascular complications or associations with subsequent doses were identified.
“Our findings support the wide uptake of future COVID-19 vaccination programmes. We hope this evidence addresses public concerns, supporting continued trust and participation in vaccination programmes and adherence to public health guidelines.”
Commenting on their paper, the authors emphasise the importance of gathering evidence on the risks and benefits of the COVID-19 vaccination programme. Dr Samantha Ip, co-author from the University of Cambridge, says that the research adds to a “large body of evidence” on the programme, which has “been shown to provide protection against severe COVID-19 and saved millions of lives worldwide”. Professor William Whiteley from the University of Edinburgh reflects that “over 90% of the population over the age of 12” received “at least one dose by January 2022”.
“This England-wide study offers patients reassurance of the cardiovascular safety of first, second, and booster doses of COVID-19 vaccines. It demonstrates that the benefits of second and booster doses, with fewer common cardiovascular events include heart attacks and strokes after vaccination, outweigh the very rare cardiovascular complications.”
Dr Venexia Walker of the University of Bristol emphasises the need to “continue to study” COVID-19 vaccines.
“The availability of population-wide data has allowed us to study different combinations of COVID-19 vaccines and to consider rare cardiovascular complications. This would not have been possible without the very large data that we are privileged to access and our close cross-institution collaborations.”
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by Charlotte Kilpatrick | Jan 24, 2024 | Technology |
In January 2024 IAVI announced a collaboration with ReiThera Srl and the Ragon Institute to develop a novel HIV vaccine candidate. This work will be funded by the Bill & Melinda Gates Foundation, with each partner bringing expertise and experience; the vaccine will comprise ReiThera’s GRAd vector and T-cell epitopes identified by the Ragon Institute. The collaboration has entered the “manufacturing phase” to produce the clinical trial material.
The partners will cover different aspect of the programme:
- ReiThera will perform vector engineering and generation, process development, and good manufacturing practice manufacture and release for the clinical use of the vaccine.
- The Ragon Insititute will lead preclinical development.
- IAVI will sponsor and execute a Phase I clinical trial to evaluate the safety and immunogenicity of the candidate.
“The research is aimed to primarily benefit those in lower- and middle-income countries, particularly in Africa, who are disproportionately impacted by HIV and lack access to suitable prevention options.”
Key partners include teams from the Africa Health Research Institute (AHRI) and the National Institute for Communicable Diseases (NICD) in South Africa and the Mutala Trust and Charles River Medical Group (CRMG) in Zimbabwe.
Ragon’s research meets ReiThera’s platform
IAVI states that “prior findings” by the Ragon Institute have shown that “mutation of residues at important network positions disproportionately impaired viral replication and occurred with high frequency in epitopes presented by protective human leukocyte antigen (HLA) class I alleles”. Furthermore, CD8+ T-cell targeting of “highly networked epitopes” distinguished people who “naturally control” HIV, even in the absence of protective HLA alleles.
The target, therefore, is the development of a vaccine component that generates a “broadly protective potent CD8 T-cell response” for “mutationally constrained” epitopes. This will be applied with ReiThera’s novel platform, which uses a proprietary replication-defective Gorilla adenoviral (GRAd) vector. This belongs to species C adenoviruses, considered “among the most potent vaccine carriers” for the purpose of inducing CD8 T-cell responses to encoded antigens, with a low seroprevalence in humans.
The platform was chosen based on evidence from preclinical and clinical studies, in which it demonstrated a “strong” induction of T-cell responses to the encoded antigens and a “very low” frequency of anti-GRAd pre-existing immunity in humans.
Dr Stefano Colloca is ReiThera’s Chief Technology Officer and co-Founder and looks forward to “collaborating with IAVI and the Ragon Institute” to continue to “advance our shared vaccine commitment to address the global challenges posed by HIV”.
“The funding validates the potential of our novel GRAd vector technology to develop vaccine candidates stimulating a strong T-cell response.”
Dr Gaurav Gaiha from the Ragon Institute is “thrilled to have the opportunity to collaborate with ReiThera and IAVI” to take the GRAd-HIV highly networked T-cell vaccine candidate “towards clinical evaluation”.
“We are particularly pleased that this takes place with partners in sub-Saharan Africa, given the immense need for new solutions to curtail the ongoing HIV epidemic.”
Dr Sangeetha Sagar, IAVI’s Vice President of Product Development, said that IAVI’s Product Development Centre (PDC) is “so pleased to be able to partner with ReiThera and the Ragon Institute”.
“The PDC’s purpose is to advance promising biomedical innovations across the global health field by supporting clinical testing and product development, and we are excited to have the opportunity to support this new approach to HIV vaccine development.”
We were glad to speak to Dr Gaiha about his efforts with the Ragon Institute at the Congress in Washington last April; you can check out his interview here. Do join us for this year’s event by getting your tickets at this link, or subscribe for more insights here.
