Using mRNA technology to develop vaccines for HIV and beyond
The initial focus of their alliance will be on the development and evaluation of mRNA vaccine formulations against human immunodeficiency virus (HIV), with the objective of identifying a lead formulation to move forward to clinical development.
An effective vaccine to prevent HIV infection has proved elusive for nearly four decades, not least because the virus constantly evolves into different strains to evade the immune system.
The parties anticipate that by combining ConserV’s and eTheRNA’s technologies, the new vaccines will induce potent immune responses to protect against highly mutagenic viruses.
ConserV claims expertise in identifying broadly-protective antigens while eTheRNA said it brings its TriMix immunostimulatory mRNA technology and novel lipid nanoparticle (LNP) encapsulation technologies to the tie-up.
Kimbell Duncan, CEO of ConserV Bioscience, commented: “Our mission is to develop safe and effective vaccines which offer broad protection against infections from viruses that mutate frequently. We are pleased to be working with eTheRNA to develop mRNA-based vaccine formulations of our antigen constructs, in combination with eTheRNA’s TriMix and LNP technologies, in order to expand our development pipeline.”
Background to the collaborators
Founded in 2020 as a spin-out from PepTcell Ltd, the Oxfordshire headquartered, ConserV, is focused on developing vaccines that protect against endemic and emergent infectious diseases. It has a pipeline of eight vaccines at various stages of pre-clinical and clinical development including candidates to protect against broad-spectrum influenza (Phase III), mosquito-borne diseases (Phase II), HIV, Hepatitis C, Hepatitis B, Rotavirus, Chagas and broad-spectrum coronavirus.
eTheRNA immunotherapies, established in January 2013 as a spin-off from the VUB university in Brussels with facilities in Niel and Ghent in Belgium, is developing immunotherapy and vaccine products for the treatment of cancer and infectious disease from its proprietary mRNA, TriMix, LNP formulation platforms.
The parties said the collaborative exercise may also develop other mRNA vaccine formulations based upon ConserV’s antigen portfolio.
ConserV's candidate antigens include conserved regions from both internal and external viral proteins containing clusters of reactive T-cell epitopes for multiple human leukocyte antigens (HLAs).
eTheRNA says its TriMix contains three mRNA molecules (caTLR4, CD40L and CD70) that, when combined, work to produce a potent, durable T-cell-mediated immune response. That biotech has also developed proprietary LNPs to be used as targeted delivery vehicles for mRNA and is developing an intranasal delivery vehicle which, combined with TriMix, aims to induce antigen-specific T-cell-mediated mucosal immunity.
HIV vaccine research - first in human clinical trial results suggest potential for novel approach
A Phase I clinical trial, IAVI G001, testing another novel vaccine approach to prevent HIV, has shown promising results.
On February 3, 2021, IAVI and Scripps Research announced that a vaccine showed success in stimulating production of rare immune cells needed to start the process of generating antibodies against the fast-mutating HIV; the targeted response was detected in 97% of participants who received the vaccine, they added.
The researchers think the approach used in this trial for HIV could also be applied to vaccines for other challenging pathogens such as influenza, dengue, Zika, and hepatitis C viruses and the malaria parasite:
“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well,” says William Schief, professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center (NAC), whose laboratory developed the vaccine.
“With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties, and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.”
The study, said the team, sets the stage for additional clinical trials that will seek to refine and extend the approach—with the long-term goal of creating a safe and effective HIV vaccine. As a next step, IAVI and Scripps Research are partnering with Moderna to develop and test an mRNA-based vaccine that harnesses the approach to produce the same beneficial immune cells. Using mRNA technology could significantly accelerate the pace of HIV vaccine development, they said.
IAVI G001 took place at two sites: George Washington University (GWU) in Washington, DC, and the Fred Hutchinson Cancer Research Center in Seattle, enrolling 48 healthy adult volunteers.
Participants received either a placebo or two doses of the vaccine compound, eOD-GT8 60mer, along with an adjuvant developed by pharma company, GSK. Dr Julie McElrath, senior VP and director of Fred Hutch’s Vaccine and Infectious Disease Division, and Dr David Diemert, professor of medicine at GWU School of Medicine and Health Sciences, were lead investigators at the trial sites.
“This is a landmark study in the HIV vaccine field, demonstrating success in the first step of a pathway to induce broad neutralizing antibodies against HIV-1,” McElrath says. “The novel design of the immunogen, the clinical trial and the molecular B cell analyses provide a roadmap to accelerate further progress toward an HIV vaccine.”
Coronavirus vaccine
ConserV also recently collaborated with the US government’s Lawrence Livermore National Laboratory (LLNL), located in California, to develop a broad-spectrum coronavirus vaccine.
That alliance, announced in January this year, looks to leverage ConserV's expertise in identifying antigens and the nanolipoprotein particle technology (NLP) delivery system of LLNL.
“We are pleased to be working with Lawrence Livermore National Laboratory to develop our broad-spectrum coronavirus vaccine candidate. We have identified regions within the proteins of the virus that are not susceptible to change and, if effective, the vaccine promises to protect against a broad spectrum of current circulating coronavirus strains and future emergent ones,” said Duncan.
