ABSTRACT
Prevention of COVID-19 is widely believed to depend on neutralization of SARS-CoV-2 by vaccine-induced humoral immunity 1,2 , raising concern that emerging escape variants may perpetuate the pandemic 3–6 . Here we show that a single intramuscular injection of Adeno-Associated Virus-6 (AAV6) or AAV9 encoding a modified, N-terminal domain deleted (ΔNTD) spike protein induces robust cellular immunity and provides long-term protection in k18-hACE2 transgenic mice from lethal SARS-CoV-2 challenge, associated weight loss and pneumonia independent of vaccine-induced neutralizing humoral immunity. In both mice and macaques, vaccine-induced cellular immunity results in the clearance of transduced muscle fibers coincident with macrophage and CD8+ cytotoxic T cell infiltration at the site of immunization. Additionally, mice demonstrate a strong Type-1 polarized cellular immunophenotype and equivalent ex vivo T cell reactivity to peptides of wt and alpha (B.1.1.7) variant spike. These studies demonstrate not only that AAV6 and AAV9 can function as effective vaccine platforms, but also that vaccines can provide long-term efficacy primarily through the induction of cellular immunity. The findings may provide an alternative approach to containment of the evolving COVID-19 pandemic and have broader implications for the development of variant-agnostic universal vaccines against a wider range of pathogens.
Subject(s)
Pneumonia , COVID-19ABSTRACT
BackgroundIt is unclear whether smoking increases the risk of COVID-19 hospitalisation. We aimed to i) examine the association of smoking status with hospitalisation for COVID-19 compared with hospitalisation for other respiratory virus infections a year previous; ii) compare current smoking in cases with age- and sex-matched London prevalence; and iii) examine concordance between smoking status recorded on the electronic health record (EHR) and the medical notes. MethodsThis retrospective case-control study enrolled adult patients (446 cases and 211 controls) at a single National Health Service trust in London, UK. London smoking prevalence was obtained from the representative Annual Population Survey. The outcome variable was type of hospitalisation (COVID-19 vs. another respiratory virus). The exposure variable was smoking status (never/former/current smoker). Logistic regression analyses adjusted for age, sex, socioeconomic position and comorbidities were performed. The study protocol and analyses were pre-registered on the Open Science Framework. FindingsPatients hospitalised with COVID-19 had lower odds of being current smokers than patients admitted with other respiratory viruses (ORadj=0.55, 95% CI=0.31-0.96, p=.04). Odds were equivocal for former smokers (ORadj=1.08, 95% CI=0.72-1.65, p=.70). Current smoking in cases was significantly lower than expected from London prevalence (9.4% vs. 12.9%, p=.02). Smoking status recorded on the EHR deviated significantly from that recorded within the medical notes ({chi}2(3)=226.7, p