COVID-19 Next Generation Vaccines: Elicio Therapeutics Launching Clinical Trials Of Its ELI-005 Immunotherapy Based Lymph Node Targeting Vaccine

COVID-19 Next Generation Vaccines: Cambridge based Elicio Therapeutics has developed a next generation COVID-19 vaccine ELI-005 that is expected to start initial clinical trials soon. Unlike most of the current genetic based vaccines under development or in phase 3 trials, this lymph node-targeting vaccine is composed of an adjuvant developed using the company’s Amphiphile technology and the SARS-CoV-2 virus’s spike protein RBD and shows promise in conferring enduring T cell immunity to COVID-19.


 
The rapid speed at which the biotech and pharmaceutical industry has responded to the SARS-CoV-2 has been phenomenal but as the same time raising skepticism in many.
 
Currently there are eight vaccines in Phase III development including those from Sinovac, Moderna, BioNTech and Pfizer, CanSinoBio, AstraZeneca and the University of Oxford, the Wuhan Institute of Biological Products, Sinopharm, and the Murdoch Children’s Research Institute.
 
Further to these eight vaccines, two controversial vaccines have been approved in Russia and China despite lack of proper phase 3 results.
 
There are growing concerns about the efficacy of these speedily developed vaccines, particularly in conferring necessary long-term T cell immunity against the SARS-CoV-2 coronavirus.
 
Furthermore with the White House most likely influencing decisions to fast track developments for political purposes and the high possibility that the vaccines will be granted fast approvals by the US FDA which are now mere puppets of the White House, often sidelining scientific based rationale for any decisions is making many previous vaccine believers to become anti-COVID-19 vaccine followers.
 
Furthermore many of the existing vaccine candidates rushed into development phases without considering emerging data and study findings.
 
Hence many other biotech firms are now focusing on what are known as next-generation vaccine approaches that could resolve these new immunity challenges.
 
Elicio Therapeutics is leveraging its Amphiphile platform, which it developed originally to treat cancer with potent lymph node-targeted immunotherapies.
 
Its next-generation Covid-19 vaccine candidate, ELI-005, is a protein subunit vaccine that targets the lymph nodes.
 
The ELI-005 vaccine has two components ie an Amphiphile adjuvant called ELI-004 and a Covid-19 spike protein receptor binding domain (RBD) and has recently completed a pre-clinical trial in mice.
 
Study findings from the pre-clinical study of ELI-005 in mice were published on a preprint server and have been submitted for peer review. https://www.biorxiv.org/content/10.1101/2020.08.17.251728v1
 
The ELI-005 vaccine utilizes a protein-based vaccination approach; similar to pneumonia and human papillomavirus vaccines and it relies on a special adjuvant developed using the company’s Amphiphile platform called ELI-004.
 
Elicio Therapeutics Inc executive vice-president and head of research and development Professor Dr Christopher Haqq told Thailand Medical News, “Adjuvants are really key s uperchargers of the immune system and they only work inside the lymph nodes.”
 
Dr Haqq added, “Elicio’s adjuvant ELI-004 for this vaccine has efficient lymph node targeting because it is able to hitchhike and piggyback on a common protein called albumin. It rides that wave of albumin in lymph channels until it reaches the lymph node,”
 
Dr Haqq notes that when the adjuvant reaches the lymph node, it turns on “the antigen presenting cells known as dendritic cells to create an immune response”. These dendritic cells are good at both presenting the antigen and at engaging with immune cells both T and B cells to coordinate the response to the pathogen.
 
The study team has already observed that dendritic cells know to target the immune cells against SARS-CoV-2 specifically since Elicio has used the virus’s spike protein RBD.
 
Dr Haqq explained, “We chose the spike RBD because other groups had already shown that it’s a great target for T cell responses, as well as antibody response, and we wanted to be able to have the best of both worlds: killer T cells as well as antibodies.”
 
The results of the pre-clinical study according to Dr Haqq showed the highest magnitude of T cell protection from mouse experiments than the team had seen with any other approach. In the experiments, the team got 25-fold higher numbers of T cells in the peripheral blood” than benchmark vaccines.
 
Significantly ELI-005 also elicited a high number of T cells compared to the benchmarks in the lung, where SARS-CoV-2 enters the body.
 
Dr Haqq stressed,“The T cells went both into the overall tissue of the lung ie  the parenchyma as well as the secretions of the lungs or the bronchoalveolar lavage fluid.”
 
Dr Haqq notes that the benchmark vaccines are two different adjuvants ie an aluminium salt called alum that is used in multiple vaccine approaches for COVID-19 and other infectious diseases, as well as a soluble version of the “same adjuvant that use in the Amphiphile format”, CPG.
 
Dr Haqq added, “Of course, they’re not exactly the same as other candidates for COVID-19, but they’re sort of generic versions of the approaches that are commonly used in the whole field of vaccination.”
 
Dr  Haqq notes that studies have shown that optimal SARS-CoV-2 vaccines must produce a particular type of T cell response ie the T helper type 1 (Th1) response. The MERS and SARS outbreaks revealed how important the Th1 response is and the danger that different T cells responses have on inflammation in the lungs of patients.
 
Dr Haqq further explained, “We were careful to look also to see that the vaccine can make a Th1 response we are really happy to see this was the case for our vaccine.”
 
One of the reasons  to adapt and incorporate the immunotherapy approach to COVID-19 vaccine  because Elicio also thought it had something to offer because studies, such as one by Dr Jose Mateus published in the journal Science in early August, had shown that “individuals that were never exposed to Covid-19 may have T cells that can cross-recognize SARS-CoV-2 because of cross-reactivity from other common cold coronaviruses” https://science.sciencemag.org/content/early/2020/08/04/science.abd3871
 
Dr  Haqq further added “Our  ELI-005 vaccine] has this really unique high magnitude T cell response that suggests that it might be able to activate those pre-existing T cells that can cross-recognize Covid-19.”
 
This according to him might able to provide people with both immediate protection and a long-term response.
 
Dr Haqq also notes this cross-reactivity with common cold viruses creating a potentially “pre-formed” T cell response against Covid-19 may mean that “there is some level of protection after the first dose” of ELI-005.
 
Dr Haqq however explained that the plan would be to give two doses to humans, as Elicio has done in the pre-clinical study in mice. This is because the second dose means the immune response switches from making Immunoglobulin M (IgM) antibodies to making Immunoglobulin G (IgG) antibodies.
 
Dr Haqq explained, “IgMs are great, but often the IgGs have a stronger binding constant and so might provide an even better response.”
 
The company is very much on track to advance to clinical trials of ELI-005 following discussions with regulators.
 
Elicio is also already thinking ahead about its manufacturing of the product.
 
Elicio already has its adjuvant ready in a good manufacturing practice format but it needs to figure out how to produce the spike protein RBD portion of the vaccine. 
 
Also Dr Haqq explained that another benefit of Elicio’s protein-based vaccine is that “Its Amphiphile molecule is quite stable, so it is anticipated that the company might be able to ship this at room temperature”.

This benefit compares favorably to the DNA and RNA approaches being developed by other companies including Moderna and Inovio which “might be less stable” and need to be shipped cold, creating huge challenges for rural health settings in developing countries.
 
Most people also think that it will be the second of third generation vaccines that will be truly effective against the COVID-19.
 
For more on COVID-19 Next Generation Vaccines, keep on logging to Thailand Medical News.