Innate immune mechanisms of mRNA vaccines.

The lipid nanoparticle (LNP)-encapsulated, nucleoside-modified mRNA platform has been used to generate safe and effective vaccines in record time against COVID-19. Here, we review the current understanding of the manner whereby mRNA vaccines induce innate immune activation and how this contributes to protective immunity. We discuss innate immune sensing of mRNA vaccines at the cellular and intracellular levels and consider the contribution of both the mRNA and the LNP components to their immunogenicity. A key message that is emerging from recent observations is that the LNP carrier acts as a powerful adjuvant for this novel vaccine platform. In this context, we highlight important gaps in understanding and discuss how new insight into the mechanisms underlying the effectiveness of mRNA-LNP vaccines may enable tailoring mRNA and carrier molecules to develop vaccines with greater effectiveness and milder adverse events in the future.

Responding to the need for online collective intelligence facilitation: A framework for systems thinking facilitators

The present article discusses the need for online collective intelligence (CI) facilitation. This article addresses the move to online spaces by proposing a reflective framework for action to orient systems thinking practitioners to the task of online CI facilitation. Consistent with models focused on the orchestration of computer-supported collaborative learning, the framework is grounded in the assumption that CI facilitators have preexisting tools, methods and skills they need to re-engineer to facilitate design teams working together online. To delineate the framework, this article focuses on the issues of tool, method and competency transfer. The framework emerges after reflection on recent efforts to implement our systems thinking methodology online with an international design team working in the area of higher education. It is hoped that this framework supports ongoing reflective dialogue and design thinking amongst CI facilitators that seek to support teams online. Finally, CI competency framework emphasizes mastery. Mastery refers to activities such as the practice of mindfulness and adaptability during a CI session, the exercise of hopefulness, courage and resilience and the ability to recover and find sources of rejuvenation between CI projects. The new reality of working online in response to COVID-19 implies that these mastery competencies are more important than ever. The world of work is moving online, and workplaces need to be adaptable. The move to online spaces has implications for teamwork and system design efforts. This paper presents a reflective framework for action to orient systems thinking practitioners to the task of online facilitation. The framework highlights the issues of tool, method and competency transfer and the need to reflect on how best to reengineer systems thinking and collective intelligence processes to facilitate design teams working together in online environments. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The impact of COVID-19 on surgical education: perspectives from Canadian general surgery residents.

Most institutions have mitigated the impact of the COVID-19 pandemic on residency education by transitioning to web-based educational platforms and using innovative solutions, such as surgical video libraries, telehealth clinics, online question banks via social media platforms, and procedural simulations. Here, we assess the perceived impact of COVID-19 on Canadian surgical residency education and discuss the unique challenges in adapting to a virtual format and how novel training methods implemented during the pandemic may be useful in the future of surgical education.

mRNA Vaccines in the COVID-19 Pandemic and Beyond.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform.

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.

The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 µg are immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.

The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.