Mitigating Covid-19 in the face of emerging virus variants, breakthrough infections and vaccine hesitancy.

The emergence and rapid global spread of the new Delta and, more recently, Omicron variants of SARS-CoV-2 pose a daunting public health emergency. Being an RNA virus, the Covid-19 virus is continuing to mutate, resulting in the emergence of new variants with high transmissibility, such as the recently discovered Omicron variant. In this paper, we consider the conditions that may facilitate viral mutations and the emergence of variants with the ability to evade immunity. Here, we have discussed the importance of vaccination with the currently available vaccines. These vaccines are highly effective at preventing serious disease, hospitalization, and death from Covid-19. However, the antibody response induced by these vaccines is short-lasting and there are reports of breakthrough infections. A stable and persistent interaction between T follicular helper cells and germinal center B cells is needed for robust B cell memory response. We discussed the potential reasons behind the breakthrough infections and underscored the importance of developing better second-generation vaccines that may not necessitate frequent booster immunizations and are preventive in nature. This may involve the development of multivalent vaccines and creating vaccines against other viral proteins including conserved proteins. Vaccine hesitancy remains a notable hurdle for implementing vaccination. Furthermore, we recommend different approaches to increase vaccine acceptance, which is a critical translational component of a successful vaccine strategy. These perspectives on overcoming the pandemic's current challenges provide strategies to contain SARS-CoV-2 globally.

Long Covid: Untangling the Complex Syndrome and the Search for Therapeutics.

Long Covid can affect anyone who has previously had acute COVID-19. The root causes of this syndrome are still unknown, and no effective therapeutics are available. This complex syndrome, with a wide array of symptoms, is still evolving. Given the dire situation, it is important to identify the causes of Long Covid and the changes occurring within the immune system of affected patients to figure out how to treat it. The immune system intersects with the persistent viral fragments and blood clots that are implicated in this syndrome; understanding how these complex systems interact may help in untangling the puzzling physiopathology of Long Covid and identifying mitigation measures to provide patients some relief. In this paper, we discuss evidence-based findings and formulate hypotheses on the mechanisms underlying Long Covid's physiopathology and propose potential therapeutic options.

Efforts at COVID-19 Vaccine Development: Challenges and Successes.

The rapid spread of SARS-CoV-2, the new coronavirus (CoV), throughout the globe poses a daunting public health emergency. Different preventive efforts have been undertaken in response to this global health predicament; amongst them, vaccine development is at the forefront. Several sophisticated designs have been applied to create a vaccine against SARS-CoV-2, and 44 candidates have already entered clinical trials. At present, it is unclear which ones will meet the objectives of efficiency and safety, though several vaccines are gearing up to obtain emergency approval in the U.S. and Europe. This manuscript discusses the advantages and disadvantages of various vaccine platforms and evaluates the safety and efficacy of vaccines in advance stages. Once a vaccine is developed, the next challenge will be acquisition, deployment, and uptake. The present manuscript describes these challenges in detail and proposes solutions to the vast array of translational challenges. It is evident from the epidemiology of SARS-CoV-2 that the virus will remain a threat to everybody as long as the virus is still circulating in a few. We need affordable vaccines that are produced in sufficient quantity for use in every corner of the world.

A review of Zika virus: hurdles toward vaccine development and the way forward.

The Zika virus (ZIKV) epidemic has recently emerged as a public health threat due to its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome (GBS). To date, no approved antiviral therapeutics to treat, nor vaccines to prevent, ZIKV infection are available. In order to develop effective anti-ZIKV vaccines, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. In this paper, we discuss the recent progress in developing vaccines against ZIKV and the hurdles to overcome in making efficacious anti-ZIKV vaccines. Here, we propose strategies to make efficacious and safe vaccines against ZIKV by using novel approaches including molecular attenuation of viruses and TLR-based nanoparticle vaccines. The question of exacerbating dengue virus infection or causing GBS through the production of cross-reactive immunity targeting viral or host proteins have been addressed in this paper. Challenges in implementing immunogenic and protective ZIKV vaccine trials in immunodepressed target populations (for example, pregnant women) have also been discussed.

CD4+ T cells from multiple sclerosis patients respond to a commensal-derived antigen.

Multiple sclerosis, an immune-mediated disease of the central nervous system, is characterized by the impaired function of regulatory cells that fail to suppress self-reactive effector cells. We have previously found that polysaccharide A, a capsular antigen derived from the human gut commensal Bacteroides fragilis, can induce a population of regulatory T cells. Herein, we demonstrate that naïve T cells isolated from patients with multiple sclerosis have the capacity to acquire regulatory characteristics when stimulated in vitro with polysaccharide A. This study demonstrates the amplification of a regulatory T cell response by a gut-derived commensal antigen in those with multiple sclerosis.

Alteration of CD39+Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment.

While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39+ Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4+CD39+ Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb. Thus, anti-CD52 can affect multiple immune mediated pathways involved in the pathogenesis of EAE/MS.