First identified as the etiological agent behind Acquired Immunodeficiency Syndrome (AIDS) in the early 1980s, HIV-1 has continued to spread into a global pandemic and major public health concern. Despite the success of antiretroviral therapy at reducing HIV-1 viremia and preventing the dramatic CD4+ T-cell collapse, infected individuals remain HIV positive for life. Unfortunately, it is increasingly clear that natural immunity is not, and may never be, protective against this pathogen. Therefore, efficacious vaccine interventions, which can either prevent infection or eradicate the latent viral reservoir and effect cure, are a major medical priority. Here we describe the development of a safe vaccine platform, currently being utilized in on-going prophylactic and therapeutic preclinical studies and consisting of highly heterogeneous virus-like particle formulations that represent the virus diversity within infected individuals. These VLPs contain no 5′LTR, no functional integrase, and have a severely mutated stem loop 1—thereby preventing any potential reverse transcription, integration, and RNA packaging. Furthermore, we demonstrate that these VLPs are morphologically identical to wild-type virus with polyvalent Env in a functional form. Finally, we show that the VLPs are antigenic and capable of generating strong immune recall responses.

Background During combined anti-retroviral treatment, a latent HIV reservoir persists within resting memory CD4 T cells that initiates viral recrudescence upon treatment interruption. Strategies for HIV-1 cure have largely focused on latency reversing agents (LRAs) capable of reactivating and eliminating this viral reservoir. Previously investigated LRAs have largely failed to achieve a robust latency reversal sufficient for reduction of latent HIV pool or the potential of virus-free remission in the absence of treatment. Methods We utilize a polyvalent virus-like particle (VLP) formulation called Activator Vector (ACT-VEC) to ‘shock’ provirus into transcriptional activity. Ex vivo co-culture experiments were used to evaluate the efficacy of ACT-VEC in relation to other LRAs in individuals diagnosed and treated during the acute stage of infection. IFN-γ ELISpot, qRT-PCR and Illumina MiSeq were used to evaluate antigenicity, latency reversal, and diversity of induced virus respectively. Findings Using samples from HIV + patients diagnosed and treated at acute/early infection, we demonstrate that ACT-VEC can reverse latency in HIV infected CD4 T cells to a greater extent than other major recall antigens as stimuli or even mitogens such as PMA/Iono. Furthermore, ACT-VEC activates more latent HIV-1 than clinically tested HDAC inhibitors or protein kinase C agonists. Interpretation Taken together, these results show that ACT-VEC can induce HIV reactivation from latently infected CD4 T cells collected from participants on first line combined antiretroviral therapy for at least two years after being diagnosed and treated at acute/early stage of infection. These findings could provide guidance to possible targeted cure strategies and treatments. Funding NIH and CIHR

Objective: Investigate the importance of optical symptoms within SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) patients. Design: Systematic review Methods: Databases searched included Medline, EMBASE, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Clinicaltrials.gov, ProQuest. As well, meeting abstracts from American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology and Canadian Ophthalmological Society were also considered. Articles underwent two rounds of screening before risk of bias assessment and data extraction. Results: In total, 582 studies were identified. A total of 2064 unique SARS-CoV-2 positive patients are included in this review from 13 different studies that met the inclusion criteria. We observed that the most common ocular symptoms in patients with SARS-CoV-2 were dry eyes, chemosis, epiphora, and blurred vision. The least common symptoms included hyperemia, conjunctivitis and photophobia. Additionally, we observed a unique relationship between patients with ocular manifestations and the severity of the systemic symptoms. Conclusion: Ocular symptoms do not occur commonly among SARS-CoV-2 positive patients; however, this study displays that there is an occurrence of common ocular manifestations such as dry eyes, chemosis, epiphora, and blurred vision. Therefore, increased ocular examinations may aid in diagnosis of SARS-CoV-2 infections. ABBREVIATIONS: COVID-19 (coronavirus disease 2019), SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) ARTICLE HISTORY