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Breaking through : my life in science
\"A story of perseverance and the power of convictions from the groundbreaking immigrant scientist whose decades-long research led to the COVID-19 vaccines. Katalin Karikó had an unlikely journey. The daughter of a butcher in postwar communist Hungary, Karikó grew up in a one-room home that lacked running water, and her family grew their own vegetables. She saw the wonders of nature all around her and was determined to become a scientist. That determination eventually brought her to the United States, where she arrived as a postdoctoral fellow in 1985 with $1,200 sewn into her toddler's teddy bear and a dream to remake medicine. Karikó worked in obscurity, battled cockroaches in a windowless lab, and faced outright derision and even deportation threats from her bosses and colleagues. She balked as prestigious research institutions increasingly conflated science and money. Despite setbacks, she never wavered in her belief that an ephemeral and underappreciated molecule called messenger RNA could change the world. Karikó believed that someday mRNA would transform ordinary cells into tiny factories capable of producing their own medicines on demand. She sacrificed nearly everything for this dream, but the obstacles she faced only motivated her, and eventually she succeeded. Karikó's three-decades-long investigation into mRNA would lead to a staggering achievement: vaccines that protected millions of people from the most dire consequences of COVID-19. These vaccines are just the beginning of mRNA's potential. Today, the medical community eagerly awaits more mRNA vaccines-for the flu, HIV, and other emerging infectious diseases. Breaking Through isn't just the story of an extraordinary woman-it's an indictment of closed-minded thinking and a testament to one woman's commitment to laboring intensely in obscurity-knowing she might never be recognized in a culture that is more driven by prestige, power, and privilege-because she believed her work would save lives\"-- Provided by publisher.
Book
Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults
In a placebo-controlled, phase 2–3 trial, one dose of mRNA-1345 led to a lower incidence of RSV disease among adults 60 years of age or older. Solicited local and systemic adverse reactions occurred more often with the vaccine.
Journal Article
mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases
In the prevention and treatment of infectious diseases, mRNA vaccines hold great promise because of their low risk of insertional mutagenesis, high potency, accelerated development cycles, and potential for low-cost manufacture. In past years, several mRNA vaccines have entered clinical trials and have shown promise for offering solutions to combat emerging and re-emerging infectious diseases such as rabies, Zika, and influenza. Recently, the successful application of mRNA vaccines against COVID-19 has further validated the platform and opened the floodgates to mRNA vaccine’s potential in infectious disease prevention, especially in the veterinary field. In this review, we describe our current understanding of the mRNA vaccines and the technologies used for mRNA vaccine development. We also provide an overview of mRNA vaccines developed for animal infectious diseases and discuss directions and challenges for the future applications of this promising vaccine platform in the veterinary field.
Journal Article
Revolutionizing immunization: a comprehensive review of mRNA vaccine technology and applications
Messenger RNA (mRNA) vaccines have emerged as a transformative platform in modern vaccinology. mRNA vaccine is a powerful alternative to traditional vaccines due to their high potency, safety, and efficacy, coupled with the ability for rapid clinical development, scalability and cost-effectiveness in manufacturing. Initially conceptualized in the 1970s, the first study about the effectiveness of a mRNA vaccine against influenza was conducted in 1993. Since then, the development of mRNA vaccines has rapidly gained significance, especially in combating the COVID-19 pandemic. Their unprecedented success during the COVID-19 pandemic, as demonstrated by the Pfizer-BioNTech and Moderna vaccines, highlighted their transformative potential. This review provides a comprehensive analysis of the mRNA vaccine technology, detailing the structure of the mRNA vaccine and its mechanism of action in inducing immunity. Advancements in nanotechnology, particularly lipid nanoparticles (LNPs) as delivery vehicles, have revolutionized the field. The manufacturing processes, including upstream production, downstream purification, and formulation are also reviewed. The clinical progress of mRNA vaccines targeting viruses causing infectious diseases is discussed, emphasizing their versatility and therapeutic potential. Despite their success, the mRNA vaccine platform faces several challenges, including improved stability to reduce dependence on cold chain logistics in transport, enhanced delivery mechanisms to target specific tissues or cells, and addressing the risk of rare adverse events. High costs associated with encapsulation in LNPs and the potential for unequal global access further complicate their widespread adoption. As the world continues to confront emerging viral threats, overcoming these challenges will be essential to fully harness the potential of mRNA vaccines. It is anticipated that mRNA vaccines will play a major role in defining and shaping the future of global health.
Journal Article
Immunogenicity and safety of mRNA-based seasonal influenza vaccines encoding hemagglutinin and neuraminidase
Current influenza vaccines induce immune responses to hemagglutinin (HA), a surface glycoprotein of seasonal influenza viruses, but have suboptimal effectiveness. mRNA vaccines may improve protection by targeting additional antigens such as neuraminidase (NA), for which immune responses independently correlate with protection. In this phase 1/2 trial (NCT05333289), healthy adults 18–75 years were randomly assigned to receive different doses of mRNA-1020 or mRNA-1030 (encoding HA and NA at different ratios), mRNA-1010 (encoding HA), or a licensed active comparator (recombinant HA). Primary endpoints were safety and reactogenicity, and HA and NA antibody responses against vaccine-matched influenza strains. Most common local and systemic solicited ARs were injection site pain and fatigue. There were no vaccine-related serious adverse events nor significant associated safety concerns through 181 days. mRNA-1020 and mRNA-1030 elicited high HA-specific immune responses and induced NA-specific immune responses with no additional reactogenicity at equivalent dose levels beyond an mRNA-based, HA-only–containing vaccine.
Improving neuraminidase content of influenza vaccines is a major focus of vaccine development. Here the authors present safety and immunogenicity of seasonal influenza mRNA vaccine candidates simultaneously encoding hemagglutinin and neuraminidase antigens in a first in-human study.
Journal Article
From COVID-19 to Cancer mRNA Vaccines: Moving From Bench to Clinic in the Vaccine Landscape
Recently, mRNA vaccines have become a significant type of therapeutic and have created new fields in the biopharmaceutical industry. mRNA vaccines are promising next-generation vaccines that have introduced a new age in vaccinology. The recent approval of two COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) has accelerated mRNA vaccine technology and boosted the pharmaceutical and biotechnology industry. These mRNA vaccines will help to tackle COVID-19 pandemic through immunization, offering considerable hope for future mRNA vaccines. Human trials with data both from mRNA cancer vaccines and mRNA infectious disease vaccines have provided encouraging results, inspiring the pharmaceutical and biotechnology industries to focus on this area of research. In this article, we discuss current mRNA vaccines broadly in two parts. In the first part, mRNA vaccines in general and COVID-19 mRNA vaccines are discussed. We presented the mRNA vaccine structure in general, the different delivery systems, the immune response, and the recent clinical trials for mRNA vaccines (both for cancer mRNA vaccines and different infectious diseases mRNA vaccines). In the second part, different COVID-19 mRNA vaccines are explained. Finally, we illustrated a snapshot of the different leading mRNA vaccine developers, challenges, and future prospects of mRNA vaccines.
Journal Article
Computational biology and artificial intelligence in mRNA vaccine design for cancer immunotherapy
Messenger RNA (mRNA) vaccines offer an adaptable and scalable platform for cancer immunotherapy, requiring optimal design to elicit a robust and targeted immune response. Recent advancements in bioinformatics and artificial intelligence (AI) have significantly enhanced the design, prediction, and optimization of mRNA vaccines. This paper reviews technologies that streamline mRNA vaccine development, from genomic sequencing to lipid nanoparticle (LNP) formulation. We discuss how accurate predictions of neoantigen structures guide the design of mRNA sequences that effectively target immune and cancer cells. Furthermore, we examine AI-driven approaches that optimize mRNA-LNP formulations, enhancing delivery and stability. These technological innovations not only improve vaccine design but also enhance pharmacokinetics and pharmacodynamics, offering promising avenues for personalized cancer immunotherapy.
Journal Article
The tangled history of mRNA vaccines
Hundreds of scientists had worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough.
Hundreds of scientists had worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough.
Journal Article
mRNA flu shots move into trials
COVID-19 provided an opportunity to show that mRNA vaccines can work. Now, drug companies are racing to apply the technology platform for influenza.COVID-19 provided an opportunity to show that mRNA vaccines can work. Now, drug companies are racing to apply the technology platform for influenza.
Journal Article
Rise of the RNA machines – self-amplification in mRNA vaccine design
The next step in mRNA vaccine design is the application of viral-based self-amplifying mRNAs (replicons) that provide long-lasting humoral and cellular immune responses upon single, low-dose immunization.Replicons encode their own replication machinery to boost their copy numbers directly after administration in target cells, which dramatically lowers the required initial mRNA dose and may consequently reduce adverse effects in individuals.Recent advances in mRNA formulation using lipid or solid nanoparticles create opportunities for novel applications for replicons such as mucosal delivery.Replicon vaccines hold potential as a platform technology when safety aspects are properly addressed.A diverse spectrum of replicons have been developed for innovative applications such as multivalent and therapeutic cancer vaccines.
mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.
Journal Article