Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported. We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5x10^10 vp or 10^11 vp Ad26.COV2.S and in 5 participants who received placebo. We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens. We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).

Young people (YP) with neurological disabilities such as cerebral palsy are increasingly living into adulthood and require healthcare transition for services including for botulinum toxin A (BoNT‐A). We analysed medical records in the three children's hospitals in New South Wales (NSW) and identified 253 YP who are expected to transition from paediatric to adult BoNT‐A services in NSW and Australian Capital Territory during 2018–2023. A substantial proportion of these YP have additional needs that will require paediatric and adult health services to work together to improve their life‐long health outcomes.

RATIONALE: RhoA is an intracellular signal transducer of the Rho family of small GTPases. We and others have recently shown that RhoA signaling plays a critical role in the pathophysiological processes of asthma, including airway hyper-responsiveness (AHR), airway inflammation, and remodeling. Here, we sought to determine whether RhoA specifically in airway epithelial cells plays a role in allergen-induced AHR and airway inflammation. METHODS: Epithelial RhoA conditional knockout mice were generated by cross-breeding RhoAflox/flox with Sftpc-Cre mice (Sftpc-Cre; RhoAflox/flox). Cockroach allergen-induced mouse model of asthma was created by using our well-established experimental protocol, and AHR and airway inflammation were investigated. RESULTS: Compared with PBS treated mice, cockroach allergenchallenged mice showed increased AHR and inflammation with elevated levels of Th2 cytokines (IL-4, IL-5, and IL-13). The increased AHR and inflammation were further potentiated in Sftpc-Cre; RhoAflox/flox mice when compared with RhoAflox/flox control mice. Interestingly, Sftpc-Cre; RhoAflox/flox mice showed extremely lower levels of TGFb1 in the bronchoalveolar lavage fluids when compared with wild-type mice. Furthermore, these Sftpc-Cre; RhoAflox/flox mice showed the formation of ectopic inducible bronchus-associated lymphoid tissue (iBALT) in the lung. These iBALTs mainly contain B cells, T cells, and DCs as determined by immunofluorescence staining. Importantly, adoptive transfer of recombinant TGF-b1 into Sftpc-Cre; RhoAflox/flox mice before allergen challenge prevents the formation of iBALT and airway inflammation. Finally, knockdown of RhoA in airway epithelial cells abrogated cockroach allergen-induced TGF-b1 release. CONCLUSIONS: Our findings suggest that type II epithelial RhoA may protect against allergic airway inflammation and the formation of iBALT through TGF-b1. 244 Tregitopes improve murine asthma by promoting highly suppressive and antigen specific Tregs

Malignant mesothelioma (MM) is a deadly cancer with increasing incidence and no effective treatment options. We have previously constructed recombinant Fowlpox virus (FP) vectors encoding full-length survivin protein (FP-surv), which induced complete tumor regression in 40% of mice bearing subcutaneous MM. Macro- and microscopic evaluation of the tumor tissue showed that the tumors in vaccinated mice had large necrotic cores resulting from enhanced survivin-specific cytotoxic T lymphocyte (CTL). We aim to refine our novel FP vaccine by focusing on the most immunodominant survivin epitopes, thus enhancing its efficacy. We have identified additional high quality antigenic targets specifically upregulated in MM that will increase the breadth of T cell responses. We have used the EpiMatrix system to identify CD4+ and CD8+ T cell epitopes for synthesis and testing. Following T cell assays, highly immunogenic peptides will be selected that specifically stimulate CTLs, without activating T regulatory cells (Treg) that interfere with anti-cancer immune responses. We will include the selected peptides in the next-generation vaccine, FP-surv.2, which we expect to be more effective for inducing an immune response against MM cells than FP carrying the entire survivin gene (FP-surv). In addition, we anticipate that this response may include a higher number of long-lived memory T cells that can be exploited to prevent MM development in high-risk predisposed subjects.