Significance To respond better to evolving pathogens, sudden outbreaks, and individual patient needs, a flexible, safe, and efficient vaccine platform amenable to rapid production near the point of care is required. To this end, we created a fully synthetic, single-dose, adjuvant-free nanoparticle vaccine platform wherein modified dendrimer molecules nanoencapsulate antigen-expressing replicon mRNAs. Vaccines can be multiplexed and formed with multiple antigen-expressing replicons. After a single immunization, the rapid-production, contaminant-free vaccines elicit vital CD8 + T-cell and antibody responses that fully protect against lethal exposures to several deadly pathogens, including Ebola virus, H1N1 influenza, and Toxoplasma gondii . We believe this technology may allow for rapid-response vaccines with broad efficacy that reduce the number and frequency of vaccinations, and healthcare worker burden. Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii , and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8 + T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.
【저자키워드】 viruses, parasites, replicon, nanoparticle, vaccine platform,