Researchers at Henry M. Jackson Foundation (HJF), Uniformed Services University of the Health Sciences (USU), and Leidos Biomedical Research, Inc. (Leidos) have developed improvements to the effectiveness of mRNA vaccines. Such enhancements could reduce the number of doses needed for maximal protection, enhance vaccine durability, and reduce associated side effects.

Applications and Advantages

• Vaccine Durability: Natural Killer (NK) cell inhibition prevents vaccine host cell death
• Improved Effectiveness: Better protection, reduced doses, reduced side-effects
• Localized: Natural Killer (NK) cells inhibited only at sites of mRNA vaccine uptake, not systemically

Innovation Description

mRNA vaccines are constructed by creating lipid nanoparticles that contain mRNA segments coding for a vaccine antigen, a protein that triggers the body’s immune system.

When injected intramuscularly, the lipid nanoparticle delivers the mRNA into cells, which then produce the protein coded by the mRNA. B cells and T cells are released to defend against the foreign proteins upon detection. NK cells are also released to destroy cells containing the protein (Fig. 1, A1-A4).

Currently, mRNA vaccines are limited by: a) requirement of at least three doses to achieve maximal immune responses and b) the cause of substantial side effects. To address this issue, researchers at HJF, USU and Leidos have come together to develop novel mRNA vaccines that code for both vaccine antigens and for one or more proteins that inhibit NK cell function or that protect cells from killing by NK cells. Doing so expands the time during which the mRNA vaccine protein is expressed by host cells by decreasing the killing of these cells by NK cells only at sites of mRNA vaccine uptake (Fig. 1, B1-B4). The deactivation of NK cells reduces inflammatory side effects and increases maximal potential immune response.

Fig. 1: A. Standard mRNA vaccination,
           B. Invention mRNA vaccination

Inventors

• Edward Mitre, M.D., Uniformed Services University of the Health Sciences
• Elizabeth Graydon, Henry M. Jackson Foundation
• Stephen Anderson, Ph.D., Leidos Biomedical Research, Inc.

Innovation Status

Conceptualization with supported data. Please see “Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability” Front Immunol. 2023 Aug 25:14:1225025

Intellectual Property Status

A PCT application has been filed PCT/US2024/037523. Another application has been filed in Taiwan.