A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice

Abstract

BackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.MethodsWe developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.ResultsWe first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.ConclusionOur study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection.

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

“…mRNA vaccines activate the body’s immune system by delivering specific mRNA sequences and inducing host cells to synthesize specific tumor antigen proteins [ 96 , 97 , 98 ]. These antigenic proteins are presented to T cells by antigen-presenting cells, triggering specific immune responses and promoting the activation and proliferation of CD8+ T cells and CD4+ T cells [ 99 ]. mRNA vaccines also contribute to the formation of immune memory, allowing the body to remember and recognize specific tumor antigens in the long term, thereby rapidly generating a specific immune response when exposed to the same antigen again ( Figure 2 ).…”

“…Vaccines 2024, 12, 186 5 of 24 specific immune responses and promoting the activation and proliferation of CD8+ T cells and CD4+ T cells [99]. mRNA vaccines also contribute to the formation of immune memory, allowing the body to remember and recognize specific tumor antigens in the long term, thereby rapidly generating a specific immune response when exposed to the same antigen again (Figure 2).…”

Mechanism, applications and of mRNA vaccines

“…mRNA vaccine-triggered immune responses can enter three types of host cells through intramuscular, intradermal, or subcutaneous injections of the mRNA vaccine: (1) non-immune cells at the site of the injection (e.g., muscle cells and epidermal cells) [12]. cells and epidermal cells) [13]; (2) immune cells (e.g., dendritic cells and macrophages) in the tissues at the site of injection [14]; and (3) After the injected mRNA has been transported to nearby lymph nodes or the spleen by the lymphatic system, immune cells in peripheral lymphoid organs will develop [15]. after injection, mRNA vaccines can be captured by antigen-presenting cells, initiating both innate and adaptive immune responses, and fully activating humoral and cellular immunity [4].…”

Lipid Nanoparticle (LNP) Delivery Vector-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

“…mRNA vaccines activate the body's immune system by delivering specific mRNA sequences and inducing host cells to synthesize specific tumor antigen proteins [96][97][98] . These antigenic proteins are presented to T cells by antigen-presenting cells, triggering specific immune responses and promoting the activation and proliferation of CD8+ T cells and CD4+ T cells [99] . mRNA vaccines also contribute to the formation of immune memory, allowing the body to remember and recognize specific tumor antigens in the long term, thereby rapidly generating a specific immune response when exposed to the same antigen again (Figure 2).…”