Intensive research into COVID-19 vaccines and vaccine technologies has produced key findings about the best ways to develop a new generation of vaccines that confer long-term immunity against this ongoing public health threat.
The majority of vaccines to date have focused on the generation of antibody (humoral) responses mediated by B cells. We have long hypothesized that antibody-based vaccines, specifically those that target only the rapidly mutating spike (S) protein on the SARS-CoV-2 virus would be incapable of providing long-term protection or prevent transmission. This is consistent with observations over the past two years: anti-S antibody levels and immune protection against COVID-19 subsides following vaccination with currently available S-targeting vaccines. Booster shots are required as often as every few months
A Mix-and-Match Strategy
Studies have also revealed the potential of a “mix-and-match” strategy wherein vaccines based on different platforms could be given in combinations of prime/boost to increase immune protection against current and future variants such as Delta and Omicron. For example, combination of an RNA vaccine that generates strong antibody responses with a DNA or a protein-based vaccine delivered in an EDV vector with an adjuvant vaccine booster could elicit robust cellular immune responses.
Our work leverages these findings in a number of ways as we develop platforms for next-generation vaccines.
First, ImmunityBio has developed vaccines that target internal proteins of the SARS-CoV-2 virus in addition to the spike protein found on the virus surface. One such protein is the nucleocapsid (N) protein, which is more highly conserved, that is, less subject to mutation, than spike. We are also using a variety of vaccine platforms – the delivery vehicle – to optimize immune responses. These include our human adenovirus 5 (hAd5) vector with advanced modifications, which is the foundation of our COVID-19 vaccines series. This platform has the potential to generate a broader immune response, including vigorous T-cell mediated responses. The first vaccine in this series has shown a high potential for efficacy in pre-clinical studies and has already been tested in multiple trials in the U.S. and South Africa as a subcutaneous injectable formulation. In addition, we are pursuing an intranasal version of the vaccine that would maximize IgA production and mucosal immunity in order to prevent transmission of the COVID-19.
In support of the mix-and-match strategy, ImmunityBio has acquired the rights to multiple additional platforms and initiated a consortium that includes 3M Company, Amyris, Inc., Baylor College of Medicine, and the Access to Advanced Health Institute (AAHI) to develop, manufacture and scale second-generation vaccines. These vaccine platforms are based on delivery of SARS-CoV-2 antigen DNA or RNA, or proteins themselves, along with adjuvants to amplify immune responses. A vital part of our development of next-generation vaccines is thermal stability. Our goal is to develop vaccines that can be stored and transported without the extreme cold-chain requirements of first-generation RNA vaccines that have limited the practicality of their use in much of the world.
Given the continued public health threat from COVID-19 and emerging SARS-CoV-2 variants, ImmunityBio has adopted a long-term approach to developing vaccine platforms. We believe these mix-and-match components are critical to providing accessible, broad, and durable protection to populations around the world, and will be the foundation for vaccines against future pandemics.
COVID-19 Clinical Trials
hAd5 S+N Platform Prime & Boost—U.S. (COVID 4.001 and 4.005) and South Africa COVID (4.007)
SISONKE Boost Trial—South Africa (COVID 4.010)
THEMBA saRNA Vaccine Boost—South Africa (COVID 4.015) and U.S. (COVID 4.016)
PULA Trial RBD Subunit Protein with TLR Adjuvant Boost—Botswana (COVID 4.014)
We believe that the key to creating long-term immunity to the SARS-CoV-2 virus and overcoming the variants that are rapidly developing around the world is to design a vaccine that activates not only antibodies but also memory B and T cells to multiple antigens. Furthermore, room temperature-stable formulations for oral delivery have the potential to solve the cold-chain challenges of distribution, and the ability to generate mucosal IgA antibody barriers to the virus in the upper respiratory tract where it first enters the body.
Dr. Patrick Soon-Shiong’s recent testimony to the U.S. Subcommittee on Africa, Global Health, and Global Human Rights addressed the need for a more durable and broad-acting #COVID vaccine that is room-temperature stable to increase vaccination rates in Africa. Link to recording