Intravacc announces additional favorable preclinical and toxicology data for Avacc 10®, an intranasal SARS-CoV-2 candidate vaccine

 

   Intravacc, a world leader in translational research and development of preventive and therapeutic vaccines, today announced additional favorable preclinical and toxicology data for Avacc 10^®, the company’s SARS-CoV-2 intranasal candidate vaccine. These results demonstrate a reduction in upper respiratory tract viral load, broad cross protection against circulating variants of concern. and a good safety profile, allowing progression towards a phase I clinical study.

Dr. Jan Groen, Intravacc’s Chairman & CEO, comments:

“Based on our additional pre-clinical data, Avacc 10^® has the potential to reduce the spreading of the virus as well as providing broad protection against circulation variants. Combined with the favorable toxicological safety data, this puts us a good position for our Phase I clinical trial, which will commence in Q4 2022."

The first set of pre-clinical studies of Avacc 10^®, published in Frontiers of Immunology in December 2021, demonstrated high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in serum,  and the nose and lungs after two intranasal vaccinations 3 weeks apart. Avacc 10^® vaccinated hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs and histopathology showed no lesions in lungs 7 days after challenge.

The objectives of the additional pre-clinical and toxicology study of Avacc 10^® were to study the dosing, cross neutralization and safety of the intranasal vaccine. For the dosing study, mice were vaccinated intranasally with two doses of various concentrations of OMV and Spike protein. Three weeks after the last vaccination neutralizing antibodies against the SARS-CoV-2 Wuhan strain and variants of concern Delta, Gamma and Omicron were determined in the sera. High virus neutralizing antibody titers were detected against all the variant viruses. Syrian hamsters were used to study viral replication after challenge with SARS-CoV-2. A reduced viral load in throat and lungs and highly reduced lung lesions were observed in Avacc 10^® vaccinated animals exposed to placebo vaccinated, challenged animals. Furthermore, delayed transmission of Avacc 10^® vaccinated, challenged animals to placebo vaccinated animals was observed.

The purpose of the repeated dose toxicity study was to assess the safety and tolerability of Avacc 10^® when administered through the intranasal route in New Zealand White Rabbits. Animals were vaccinated 3 times with  Avacc 10^® , and control animals with OMV only, or saline buffer. Toxicity was monitored until 2 weeks after the final vaccination. No clinical signs of toxicity nor morbidity/mortality were found in any of the groups, and no gross pathological changes were observed, demonstrating the safety of OMV based vaccine. All Avacc 10^® vaccinated animals showed high IgG antibodies levels against Spike as well as virus neutralizing antibodies. 

Based on the outcome of the Phase I trial, Intravacc will seek manufacturing and commercialization license partners.

Moderna vaccine becomes third COVID-19 vaccine approved by UK regulator

  

The COVID-19 vaccine developed by Moderna has today been given regulatory approval for supply by the Medicines and Healthcare products Regulatory Agency (MHRA). This follows a thorough and rigorous assessment by the MHRA’s teams of scientists, including advice from the independent Commission on Human Medicines, which reviewed in depth all the data to ensure this vaccine meets the required standards of safety, quality and effectiveness.

This is the third COVID-19 vaccine to be approved for use by the MHRA and is the second mRNA vaccine (the Pfizer/BioNTech vaccine approved in December 2020 is also an mRNA vaccine).

MHRA Chief Executive Dr June Raine said:

“Today’s approval brings more encouraging news to the public and the healthcare sector. Having a third COVID-19 vaccine approved for supply following a robust and thorough assessment of all the available data is an important goal to have achieved and I am proud that the agency has helped to make this a reality.

“The progress we are now making for vaccines on the regulatory front, whilst not cutting any corners, is helping in our global fight against this disease and ultimately helping to save lives. I want to echo that our goal is always to put the protection of the public first.

“Once in use, all COVID-19 vaccines are continually monitored by the MHRA. This ensures that the benefits in protecting people against COVID-19 continue to far outweigh any potential side-effects.

“Meantime, even if you have had a vaccine it is vital that everyone follows the national lockdown restrictions and remembers ‘stay alert, protect the NHS and save lives’ at all times.”

Professor Sir Munir Pirmohamed, Chair of the Expert Working Group of the Independent Commission on Human Medicines said:

“We are delighted to be able to give a positive recommendation for the Moderna vaccine which will help in the roll-out of the COVID-19 vaccination programme.

“As with all the COVID-19 vaccine data we have seen to date, we have ensured a robust and thorough safety assessment has been carried out with the independent experts that sit on this group.”

Vaccine Background

This Moderna vaccine works by injecting a small part of the COVID-19 virus’ genetic code, which triggers an immune response and creates antibodies in the human body able to fight the virus. The dosage for this specific vaccine requires two doses to be given. It is recommended to administer the second dose 28 days after the first. It is approved for use in people 18 years and over, and it can be used by pregnant and breastfeeding women following a discussion with their healthcare provider on the benefits and risks. It can be stored at -20°C for up to six months.

The National Institute for Biological Standards and Control, part of the agency, is carrying out independent batch release on all of the approved vaccines, to ensure that every batch meets quality standards, and it will do so for the Moderna COVID-19 Vaccine.

In line with the other COVID-19 vaccines that have been approved, the Moderna vaccine should only be considered for use in pregnancy when the potential benefits outweigh any potential risks for the mother and baby. Women should discuss the benefits and risks of having the vaccine with their healthcare professional and reach a joint decision based on individual circumstances. Women who are breastfeeding can also be given the vaccine after a discussion with their healthcare professional.

Anyone with a previous history of allergic reactions to the ingredients of the vaccine should not receive it, but those with any other allergies such as a food allergy can have the vaccine.

  

Possibilities for personalised vaccines revealed at ESMO Symposium

The possibilities for personalised vaccines in all types of cancer are revealed today in a lecture from Dr Harpreet Singh at the ESMO Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.
“One of the biggest hurdles in cancer immunotherapy is the discovery of appropriate cancer targets that can be recognised by T-cells,” said Singh, who is scientific coordinator of the EU-funded GAPVAC phase I trial which is testing personalised vaccines in glioblastoma, the most common and aggressive brain cancer. “In the GAPVAC trial we will treat glioblastoma patients with vaccines that are ideal for each patient because they contain personalised antigens.”
For all patients in the GAPVAC study, researchers will identify genes expressed in the tumour, peptides presented on the human leukocyte antigen (HLA) receptor (i.e. peptides which will be seen by T-cells), cancer specific mutations, and the ability of the immune system to mount a response to certain antigens. Based on this information, two vaccines, called actively personalised vaccines (APVACs), will be constructed and administered following conventional surgery.
The first vaccine will be prepared from a warehouse of 72 targets previously identified by the researchers as relevant for treatment in glioblastoma. These peptides have been manufactured and put on the shelf ready to be vaccinated in patients. Patients will be given a cocktail of the peptides they express and which their immune system can mount a response to.
Singh said: “A patient may express 20 of these 72 targets on their tumour, for example. If we find that the patient’s immune system can mount responses to 5 of the 20 targets, we mix the 5 peptides and give them to the patient. We mix the peptides off the shelf but the cocktail is changed for each patient because it is matched to their biomarkers.”
The second vaccine is synthesised de novo based on a mutated peptide expressed in the tumour of the patient. Singh said: “That peptide is not in our warehouse because it just occurs in this one single patient. The patient receives APVAC-1 and APVAC-2 in a highly personalised fashion in a way that I think has never been done for any patient.”
He added: “GAPVAC has two major goals. One is to show that personalised vaccines are feasible, since this is one of the most complicated trials ever done in cancer immunotherapy. The second is to show that we can mount far better biological responses in these patients compared to vaccination with non-personalised antigens.”
Singh’s previous research has shown that vaccination with non-personalised antigens leads to better disease control and longer overall survival in phase I and phase II clinical studies in patients with renal cell cancer.²
Singh said: “For the non-personalised vaccines we used off-the-shelf peptide targets that were shared by many patients with a particular cancer. Using this approach we have successfully vaccinated patients with renal cell cancer, colorectal cancer and glioblastoma.”
He added: “During this research we identified other targets that appeared in very few patients or even, in extreme cases, in a single patient. Often these rarer peptides are of better quality, meaning they are more specifically seen in cancer cells and occur at higher levels. This led us to start developing personalised cancer vaccines which contain the ideal set of targets for one particular patient. We hope they will be even more effective than the off-the-shelf vaccines.”
Singh continued: “A very simple example from something established is trastuzumab in breast cancer. Trastuzumab was originally given to every breast cancer patient and the efficacy was just seen in a subset. Now only about 20% of breast cancer patients receive trastuzumab and the personalised aspect is just based on the low abundance of Her2, the target.”

Singh believes that personalised vaccines hold promise for all types of cancer, and that personalisation could also be applied to adoptive cell therapy.