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.

Passive Serum Therapy to Immunomodulation by IVIG: A Fascinating Journey of Antibodies.

The immunoregulatory and anti-infective properties of normal circulating polyclonal Abs have been exploited for the therapeutic purposes in the form of IVIG as well as several hyperimmune globulins. Current knowledge on the therapeutic use of normal Igs is based on the discoveries made by several pioneers of the field. In this paper, we review the evolution of IVIG over the years. More importantly, the process started as an s.c. replacement in γ globulin-deficient patients, underwent metamorphosis into i.m. Ig, was followed by IVIG, and is now back to s.c. forms. Following successful use of IVIG in immune thrombocytopenic purpura, there has been an explosion in the therapeutic applications of IVIG in diverse autoimmune and inflammatory conditions. In addition to clinically approved pathological conditions, IVIG has been used as an off-label drug in more than 100 different indications. The current worldwide consumption of IVIG is over 100 tons per year.

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.

The expanding epidemic of HIV-1 in the Russian Federation.

In a Perspective, Chris Beyrer and coauthors discuss the threat of HIV to health in the Russian Federation.

The global response to HIV in men who have sex with men.

Gay, bisexual, and other men who have sex with men (MSM) continue to have disproportionately high burdens of HIV infection in countries of low, middle, and high income in 2016. 4 years after publication of a Lancet Series on MSM and HIV, progress on reducing HIV incidence, expanding sustained access to treatment, and realising human rights gains for MSM remains markedly uneven and fraught with challenges. Incidence densities in MSM are unacceptably high in countries as diverse as China, Kenya, Thailand, the UK, and the USA, with substantial disparities observed in specific communities of MSM including young and minority populations. Although some settings have achieved sufficient coverage of treatment, pre-exposure prophylaxis (PrEP), and human rights protections for sexual and gender minorities to change the trajectory of the HIV epidemic in MSM, these are exceptions. The roll-out of PrEP has been notably slow and coverage nowhere near what will be required for full use of this new preventive approach. Despite progress on issues such as marriage equality and decriminalisation of same-sex behaviour in some countries, there has been a marked increase in anti-gay legislation in many countries, including Nigeria, Russia, and The Gambia. The global epidemic of HIV in MSM is ongoing, and global efforts to address it remain insufficient. This must change if we are ever to truly achieve an AIDS-free generation.

An action agenda for HIV and sex workers.

The women, men, and transgender people who sell sex globally have disproportionate risks and burdens of HIV in countries of low, middle, and high income, and in concentrated and generalised epidemic contexts. The greatest HIV burdens continue to be in African female sex workers. Worldwide, sex workers still face reduced access to needed HIV prevention, treatment, and care services. Legal environments, policies, police practices, absence of funding for research and HIV programmes, human rights violations, and stigma and discrimination continue to challenge sex workers' abilities to protect themselves, their families, and their sexual partners from HIV. These realities must change to realise the benefits of advances in HIV prevention and treatment and to achieve global control of the HIV pandemic. Effective combination prevention and treatment approaches are feasible, can be tailored for cultural competence, can be cost-saving, and can help to address the unmet needs of sex workers and their communities in ways that uphold their human rights. To address HIV in sex workers will need sustained community engagement and empowerment, continued research, political will, structural and policy reform, and innovative programmes. But such actions can and must be achieved for sex worker communities everywhere.

Natural autoantibodies to Fcγ receptors in intravenous immunoglobulins.

A considerable progress has been achieved in the comprehension of the cellular and molecular mechanisms that account for the therapeutic benefit of intravenous immunoglobulin (IVIg) in several autoimmune and inflammatory conditions. However, the precise mechanisms responsible for such a wide range of biological activities have not been proven unambiguously. A wide range of specificities have been identified within IVIg including idiotypes of immunoglobulins, T cell receptor, HLA molecules, several cell surface molecules of immunological importance such as CD4, CD5, Fas, BAFF, cytokines and cytokine receptors, chemokine receptors, CD40 among others. Here we identify and characterize the natural autoantibodies of IgG isotype directed against the human Fc receptors. We show that the F(ab')2 of IVIg recognize the FcγRIII (CD16) and FcγRII (CD32). Interestingly, the immunopurified anti-FcγIII and anti-FcγII antibodies isolated from IVIg bind soluble and membrane-bound FcR and inhibit rosette formation. Altogether, these results along with previous reports provide pointers on the existence of functionally relevant natural autoantibodies towards a wide range of self-motifs that may participate in regulation of the immune response. Their presence in the therapeutic immunoglobulin preparations may explain at least in part, the beneficial effect of IVIg in autoimmune diseases.