The COVID-19 pandemic, caused by infection with the SARS-CoV-2 coronavirus, is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale-up. Here, we developed an alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with Lipid InOrganic Nanoparticles (LION) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a Type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in lung and spleen. Prime-only immunization of aged (17-month old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. Importantly, in nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in 5 intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

1The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and 2 deleterious impact on health services and the global economy. Grim public health statistics highlight the 3 need for vaccines that can rapidly confer protection after a single dose and be manufactured using 4 components suitable for scale-up and efficient distribution. In response, we have rapidly developed 5 repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon 6 formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, 7 delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits 8 robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as 9 well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates 10 elicited antibody responses that potently neutralized SARS-CoV-2. These data support further 11 development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in December 2019 14 and within 3 months, Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 infection, was 15 declared a worldwide pandemic 1-3 . Coronaviruses are enveloped, single-strand positive-sense RNA 16 viruses with a large genome and open reading frames for four major structural proteins: Spike (S), 17 envelope, membrane, and nucleocapsid. The S protein mediates binding of coronaviruses to angiotensin 18 converting enzyme 2 (ACE2) on the surface of various cell types including epithelial cells of 19 the pulmonary alveolus 4-6 . Protection is thought to be mediated by neutralizing antibodies against the S 20 protein 7,8 , as most of the experimental vaccines developed against the related SARS-CoV incorporated 21 the S protein, or its receptor binding domain (RBD), with the goal of inducing robust, neutralizing 22 responses 9-11 . Indeed, previous reports have shown that human neutralizing antibodies protected mice 23 challenged with SARS-CoV 12-14 and Middle East respiratory syndrome (MERS)-CoV 15 suggesting that 24 protection against SARS-CoV-2 can be mediated through anti-S antibodies. Additionally, SARS vaccines 25 that drive Type 2 T helper (Th2) responses have been associated with enhanced lung immunopathology 26 following challenge with SARS-CoV while those with a Type 1 T helper (Th1)-biased immune response 27 are associated with enhanced protection in the absence of immunopathology 16,17 . Therefore, an 28 effective COVID-19 vaccine will likely need to induce, at the very least, Th1-biased immune responses 29 comprised of SARS-CoV-2-specific neutralizing antibodies.30 Nucleic acid vaccines have emerged as ideal modalities for rapid vaccine design, requiring only 31 the target antigen's gene sequence and removing dependence on pathogen culture (inactivated or live 32 attenuated vaccines) or scaled recombinant protein production. In a...

More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Introduction: Leprosy is a chronic disease that affects skin and peripheral nerves. Disease complications include reactional episodes and physical impairment. One World Health Organization (WHO) goal of leprosy programs is to decrease the number of grade 2 impairment diagnoses by 2015. This study aims to evaluate clinical factors associated with the occurrence of leprosy reactions and physical impairment in leprosy patients. Methods: We conducted a retrospective study of data from medical records of patients followed in two important centers for the treatment of leprosy in Aracaju, Sergipe, Brazil, from 2005 to 2011. We used the chi-square test to analyze associations between the following categorical variables: gender, age, operational classifi cation, clinical forms, leprosy reactions, corticosteroid treatment, and physical impairment at the diagnosis and after cure. Clinical variables associated with multibacillary leprosy and/or reactional episodes and the presence of any grade of physical impairment after cure were evaluated using the logistic regression model. Results: We found that men were more affected by multibacillary forms, reactional episodes, and grade 2 physical impairment at diagnosis. Leprosy reactions were detected in a total of 40% of patients and all were treated with corticosteroids. However, physical impairment was observed in 29.8% of the patients analyzed at the end of the treatment and our multivariate analysis associated a low dose and short period of corticosteroid treatment with persistence of physical impairments. Conclusions: Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.