From private incentives to public health need: rethinking research and development for pandemic preparedness.

Pandemic preparedness and response have relied primarily on market dynamics to drive development and availability of new health products. Building on calls for transformation, we propose a new value proposition that instead prioritises equity from the research and development (R&D) stage and that strengthens capacity to control outbreaks when and where they occur. Key elements include regional R&D hubs free to adapt well established technology platforms, and independent clinical trials networks working with researchers, regulators, and health authorities to better study questions of comparative benefit and real-world efficacy. Realising these changes requires a shift in emphasis: from pandemic response to outbreak control, from one-size-fits-all economies of scale to R&D and manufacture for local need, from de novo product development to last-mile innovation through adaptation of existing technologies, and from proprietary, competitive R&D to open science and financing for the common good that supports collective management and sharing of technology and know-how.

Natural IgG Anti-F (ab')2 Autoantibody Activity in Children with Autism.

Background: Many and diverse autoimmune abnormalities have been reported in children with autism. Natural autoantibodies (NAAbs) play important immunoregulatory roles in recognition of the immune self. The objective of this study was to examine the presence of NAAbs in the sera of children with autism and across severity subgroups of autistic behavioral impairments. Methods: NAAbs were titrated in sera through an ELISA procedure in 60 low-functioning children with autism and 112 typically developing controls matched for age, sex and puberty. Results: Serum titers of IgG anti-F(ab')2 autoantibodies were significantly lower in children with autism compared to typically developing controls (p < 0.0001), and were significantly negatively associated with autism severity (p = 0.0001). This data appears to be related more specifically to autism than to intellectual disability, given that IgG anti-F(ab')2 levels were significantly negatively correlated with IQ scores in the autism group (p = 0.01). Conclusions: This is the first report in autism of abnormally low natural anti-F(ab')2 autoantibody activity. The findings suggest a dysfunction of self-recognition mechanisms which may play a role in the pathogenesis of autism, especially for the severely affected children. These findings strengthen the hypothesis of an autoimmune process in autism and open the prospect of alternative medical treatment. Further neuroimmunological research is warranted to understand the exact mechanisms underlying this reduced natural IgG anti-F (ab')2 autoantibody activity, and to assess its impact on the pathophysiology and behavioral expression of autism.

Integrating HIV and substance misuse services: a person-centred approach grounded in human rights.

Integrating HIV-related care with treatment for substance use disorder provides an opportunity to better meet the needs of people living with these conditions. People with substance use disorder are rendered especially vulnerable by prevailing policies, structural inequalities, and stigmatisation. In this Series paper we analyse existing literature and empirical evidence from scoping reviews on integration designs for the treatment of HIV and substance use disorder, to understand barriers to and facilitators of care integration and to map ways forward. We discuss how approaches to integration address two core gaps in current models: a failure to consider human rights when incorporating the perspectives of people living with HIV and people who use drugs, and a failure to reflect critically on structural factors that determine risk, vulnerability, health-care seeking, and health equity. We argue that successful integration requires a person-centred approach, which is grounded in human rights, treats both concerns holistically, and reconnects with underlying social, economic, and political inequalities.

A consideration of convalescent plasma and plasma derivatives in the care of Severely-ill patients with COVID-19.

The pathogenesis and immunopathological damage of severe forms of COVID-19 resemble acute autoimmune disease sparked by SARS-CoV-2, including an early systemic overproduction of proinflammatory cytokines. Such immunopathological features provide a rationale for the use of passive immunotherapy with convalescent plasma as a source of neutralizing anti-viral antibodies and of anti-inflammatory plasma components. While convalescent plasma therapy is now being evaluated in prospective clinical trials, we further consider the therapeutic potential of human hyper immune globulins, and of heterologous, engineered and monoclonal neutralizing antibodies as anti-viral agents to treat COVID-19. Good medical practice procedures are still needed and is why we also discuss the potential use of polyclonal polyspecific immunoglobulins (IVIG), a therapeutic plasma derivative, with potent anti-inflammatory activity, in severe forms of Covid-19.

Antibody-based therapies for COVID-19: Can Europe move faster?

Michel Goldman and colleagues call on the European medical and scientific community to coordinate efforts on immunotherapy-based approaches to coronavirus.

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis.

Natural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases.

Getting to grips with the HIV epidemic in Russia.

PURPOSE OF REVIEW: In contrast to global patterns, the HIV epidemic in the Russian Federation continues to expand. The epidemic remains largely concentrated among key populations and their sexual partners but has the potential of affecting the general population. We have focused our analysis on legislative, policy-related, structural, and cultural obstacles that the country faces in confronting its epidemic. RECENT FINDINGS: The Russian Federation has the largest HIV epidemic in Europe. Recent epidemiological analyses have shown a decrease in the annual growth of new reported infections. However, stigma and discrimination, marginalization, legislative provisions, harsh policing, and the lack of relevant prevention programs remain compounding factors that limit access of at-risk populations to information, prevention, and care, including to treatment for a number of people who would know their serological status. SUMMARY: The ability of the Russian Federation to address the challenges it faces in dealing with a concentrated epidemic, will determine the future of the epidemic in the country.