Tech #1343: ImmunoTargeting Vaccine Platform

Jean-Philippe Julien, The Hospital for Sick Children

Our interconnected world enables rapid spread of emerging infectious diseases and variants, highlighting the need for efficient, adaptable vaccine development platforms.

Despite vaccine successes, the recent pandemic has revealed gaps and challenges, including the need for: 1) Rapid and less costly vaccine development, 2) Modular platforms with broad neutralizing capabilities against the newest strains and diseases, 3) Stronger B cell responses to prevent initial infection, and 4) Vaccines that don’t require extreme cold chain storage.

Jean-Philippe Julien and Brian Barber created a vaccine platform from a fully humanized monoclonal antibody recognizing HLA-DR, called the ImmunoTargeting Vaccine (ITV) (Figure 1). The platform is a modular, adjuvant-free, pan-HLA-DR-immunotargeting subunit vaccine with broad HLA-DR reactivity for effectiveness across diverse human populations (Figure 2). The ITV was created with the challenges above in mind:

1. The adjuvant-free formulation bypasses complex, timely, and expensive processes of developing a new adjuvant, or testing new antigens with established adjuvants. With platform vaccines, the issue is amplified, as the adjuvant must be tested with each antigen alone, and then with the full combination of antigens.
2. The antibody can be fused to up to four different cargo, including antigens and t-cell stimulatory peptides. The modular nature of the platform allows for multivalency and could address antigenic drift.
3. The pan-HLA-DR monoclonal antibody (44H10) delivers viral antigens directly to antigen-presenting cells, eliciting antigen uptake and strong B-cell responses. The additional incorporation of T-cell epitopes facilitates a broader, longer-lasting immune response.
4. The thermostability simplifies storage and distribution, suitable for rural locations and LMICs.

We believe ITV could address vaccine shortcomings and improve immune responses, especially in the most vulnerable (elderly, immunocompromised, cancer patients, non-responders), who often have weaker and rapidly waning antibody protection. It also offers pandemic preparedness by quickly engineering multiple antigens onto the platform, for broad, multivalent immune responses, with potential as both a primary vaccine series and a booster for infectious diseases.

ITV engineered to carry the RBD domain of both SARS-CoV-2 and SARS-CoV-1 has demonstrated pre-clinical POC both in in vitro PsV assays and in an in vitro rabbit model of infection (Figures 3 and 4).

The platform is well-evaluated in adjuvant free settings and is ready for more intensive studies evaluating the potential to boost the immune response in the vulnerable.