Self-amplifying RNA vaccines for infectious diseases
GENE THERAPY
Authors: Bloom, Kristie; van den Berg, Fiona; Arbuthnot, Patrick
Abstract
Vaccinology is shifting toward synthetic RNA platforms which allow for rapid, scalable, and cell-free manufacturing of prophylactic and therapeutic vaccines. The simple development pipeline is based on in vitro transcription of antigen-encoding sequences or immunotherapies as synthetic RNA transcripts, which are then formulated for delivery. This approach may enable a quicker response to emerging disease outbreaks, as is evident from the swift pursuit of RNA vaccine candidates for the global SARS-CoV-2 pandemic. Both conventional and self-amplifying RNAs have shown protective immunization in preclinical studies against multiple infectious diseases including influenza, RSV, Rabies, Ebola, and HIV-1. Self-amplifying RNAs have shown enhanced antigen expression at lower doses compared to conventional mRNA, suggesting this technology may improve immunization. This review will explore how self-amplifying RNAs are emerging as important vaccine candidates for infectious diseases, the advantages of synthetic manufacturing approaches, and their potential for preventing and treating chronic infections.
Respiratory Syncytial Virus Outbreak in a Veterans Affairs Long-term Care Facility
INFECTIOUS DISEASES IN CLINICAL PRACTICE
Authors: Barrett, Nancy; Bailey, Lisa; Ford, Florence; Thorne, Monique; Azab, Nancy; LeMaitre, Beth; Lobo, Zeena; Psevdos, George
Abstract
Background Respiratory syncytial virus (RSV) is increasingly becoming an important cause of respiratory infections in adults, especially those living in long-term care facilities (LTCFs). Seasonal outbreaks peaking from October to April are common. We report an outbreak of RSV involving 2 LTCFs with total capacity of 80 beds in 2019. Methods Retrospective chart review of cases identified with positive RSV infection via DNA polymerase chain reaction (PCR) from January 24 to February 24, 2019, at 2 LTCF units, in close proximity to each other, at Northport Affairs Medical Center. Results Twenty veterans (18 men and 2 women) tested positive for RSV by rapid PCR. The median age was 73 (47-89) years, 85% are Caucasian, and 5 patients had temperature of greater than 100 degrees F (100 degrees F-102.4 degrees F). All had rhinorrhea and 65% had cough. Medical history shows 45% with dementia, 30% with stroke, and 35% with diabetes; 2 patients on hemodialysis; and 2 patients with chronic obstructive pulmonary disease (COPD). Four patients required hospitalization, and 2 of them required admission to intensive care unit. Length of stay ranged from 1 to 9 days. One patient with COPD required mechanical ventilation. One patient with computed tomography finding of airway impaction had antibiotics stopped by infectious diseases consult, yet he developedClostridium difficilediarrhea. No deaths were observed, and all patients recovered. Aggressive infection control measures were implemented. Conclusions Respiratory syncytial virus is highly infectious and can easily cause an outbreak in an LTCF. Polymerase chain reaction testing was contributory to identify cases rapidly. Rapid PCR results and intensified infection control measures were instrumental to halt the outbreak.