Perhaps more than any other medical discovery, vaccines have changed the course of infectious diseases and human history. Because of vaccines, smallpox has been eradicated throughout the world, and polio significantly curbed. In the United States, vaccines have nearly eradicated diphtheria, bacterial influenza, measles, mumps, rubella, and tetanus. But, as new infectious agents are constantly emerging—and old ones constantly evolving to outsmart and elude current vaccines—researchers are looking to the development of universal vaccines to help in the never-ending battle between infectious agents and mankind. Universal vaccines have the potential to alter the spread, prevalence, and management of infectious diseases. Imagine the implications of developing a universal vaccine against pathogens such as Staphylococcus aureus, Pseudomonas spp., Acinetobacter baumannii, and Escherichia coli—the causes of nosocomial infections that range from urinary tract infections to septicemia, sickening millions worldwide and boasting not only high mortality rates, but the ability to evolve to develop antibiotic resistance. Or, imagine a universal vaccine for fungal infections, a particular concern for immunocompromised patients. Researchers are working on developing several universal vaccines that are broadly protective. Their efforts have been aided by our ever-advancing knowledge of DNA sequencing. “The ability to sequence the genomes of microorganisms has been a quantum leap in the ability to mine the microbial blueprint and discover conserved antigens that could not be identified by other technologies,” wrote Antonio Cassone, MD, professor of medical microbiology, Department of Infectious, Parasitic, and Immunomediated Diseases, Istituto Superiore di Sanita, Rome, Italy, and Rino Rappuoli, global head, Vaccines Research, Novartis Vaccines and Diagnostics, Siena, Italy, in an mBio perspective. “There is now hope, sustained by knowledge and technology, for the generation of broadly protective ‘universal’ vaccines restricted to species or groups of closely related pathogens or even cross-family or -kingdom vaccines. Overall, it is time to address a new strategy for vaccination based on antigenic commonalities for cross-protective vaccine production,” the authors noted. To this end, researchers are currently hard at work developing a universal influenza vaccine and a universal strep throat vaccine. Universal influenza vaccine In early April 2019, researchers began the first clinical trial of a new universal influenza vaccine. Endpoints will include safety, tolerability, and the vaccine’s ability to induce an immune response in healthy volunteers. The experimental vaccine they will be studying is known as H1ssF_3928, and was developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health. They engineered H1ssF_3928 as part of a research effort to develop a universal flu vaccine capable of providing durable protection from several flu subtypes in people of all ages. The experimental vaccine is designed to cue the body to mount protective immune responses to many flu subtypes. To do this, the vaccine was designed to focus the immune system on a component of the virus that changes very little from strain to strain. “Seasonal influenza is a perpetual public health challenge, and we continually face the possibility of an influenza pandemic resulting from the emergence and spread of novel influenza viruses,” said NIAID director Anthony S. Fauci, MD. “This phase 1 clinical trial is a step forward in our efforts to develop a durable and broadly protective universal influenza vaccine.” Influenza vaccines must be updated annually because the hemagglutinin (HA) head of the influenza virus is subject to antigenic drift, changing constantly. HA is comprised of a head and a stem. H1ssF_3928 displays only the stem of the influenza protein HA on its vaccine platform. The HA stem is less subject to antigenic drift and, therefore, less likely to change. Based on the stem of an H1N1 influenza virus, the stem used on the candidate vaccine allows for hope that the vaccine will not need annual updating with each coming flu season. Further, researchers have hypothesized that targeting the HA stem without the HA head may induce broader and longer immunity. This phase 1 study is based on data from previous work, in which researchers assessed a ferritin nanoparticle vaccine that included both the HA head and stem. Ferritin, a natural protein found in cells from all living species, will be the platform for this new vaccine candidate, and was shown—in the previous study—to be safe and well-tolerated in humans. Universal strep throat vaccine In addition to the universal influenza vaccine, researchers are also developing a universal strep throat vaccine. Streptococcus pyogenes, also known as group A streptococcus, causes strep throat, which affects 3 out of 10 children with a sore throat, according to the CDC. It is especially common in children aged 3 to 15 years. Because strep throat is highly contagious, children infected with strep throat cannot attend school during the early stages of infection. There is currently no vaccine for group A streptococcus. But, researchers from the University of California San Diego (UCSD) School of Medicine, San Diego CA, are working to develop a universal strep throat vaccine with SutroVax, Inc., Foster City, CA. Their work is based on research led by Victor Nizet, MD, professor, Departments of Pediatrics and Pharmacy, UCSD, and colleagues. “Most people experience one or more painful strep throat infections as a child or young adult,” said Dr. Nizet. “Developing a broadly effective and safe strep vaccine could prevent this suffering and reduce lost time and productivity at school and work, estimated to cost $2 billion annually.” Dr. Nizet and colleagues identified the role of the Lancefield antigen in the pathogenesis of group A streptococcus. Their findings also reveal how Streptococcus resists the immune system, and laid the foundation for a new strategy for a strep throat vaccine. “In this study, we discovered the strep genes responsible for the biosynthesis and assembly of group A carbohydrate (GAC), the very molecule that defines the pathogen in clinical diagnosis,” said first author Nina M. van Sorge, PharmD, PhD, a former postdoctoral fellow, UCSD, who now leads her own laboratory at Utrecht University Medical Center, Netherlands. “This discovery allowed us to generate mutant bacterial strains and study the contribution of GAC to strep disease.” Their findings may be the foundation of a new, universal vaccine against strep throat, necrotizing fasciitis, and rheumatic heart disease. Although it seems distant, the development of successful universal vaccines is well underway, and may—someday—put us in the lead in the fight between man and pathogen. “There is now hope, sustained by knowledge and technology, for the generation of broadly protective “universal” vaccines restricted to species or groups of closely related pathogens or even cross-family or -kingdom vaccines. Overall, it is time to address a new strategy for vaccination based on antigenic commonalities for cross-protective vaccine production,” concluded Dr. Cassone and Rappuoli. Dr. Nizet’s study was funded, in part, by the National Institutes of Health, including the UC San Diego Program in Excellence in Glycosciences, the Australian National Health and Medical Research Council, the Wellcome Trust, and the Netherlands Organization for Scientific Research. Source
