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.

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.

Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected AJJ mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg-and PTgB-infected A/J mice exhibited a significant reduction in the concanavalin A (Con A)-induced lymphoproliferative response. Further, the response of splenocytes from mice infected with the wild-type parasite was significantly diminished compared with that of mice infected with PTgB. The lymphoproliferative response to Con A reached its nadir at day 7 and remained below control levels for at least 14 days postinfection. By day 21 postinfection, the response to Con A and to Toxoplasma antigens was restored to the level observed prior to day 7. Con A-stimulated culture supernatants of spleen cells from mice on day 7 postinfection contained significantly less IL-2 than pormal mice. There was no significant difference in the numbers of binding sites or capacity of high-affinity IL-2 receptors between infected and normal mouse splenocytes as determined by Scatchard analysis. Exogenous IL-2 at different concentrations failed to restore the proliferative response of lymphocytes from infected mice to Con A. Adherent macrophages from 7-day-infected mice were able to suppress IL-2 production by normal splenocytes following stimulation with Con A. The inhibitory activity mediated by infected cells was reversed by the antibody to IL-10 but not transforming growth factor [B. There were insignificant levels of nitric oxide production in both infected and normal splenocytes. These results indicate that during acute murine toxoplasmosis, there is a well-defined period (day 7) during which both the T-cell mitogen and parasite antigen-associated lymphoproliferative response are reduced. Further, there is a reduction in the production of IL-2 and an increase in IL-10, which appear to mediate, in part, the observed downregulation of immunity to T. gondii.

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c Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre-and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients.

We recently showed that B cells reduce CNS inflammation in mice with experimental allergic encephalomyelitis (EAE). Here, we demonstrate that adoptively transferred CD5/CD19+ B cells protect against EAE severity. Furthermore, we show that glatiramer acetate (GA), a therapeutic for relapsing multiple sclerosis treatment, amplifies this effect. Transfer of GA-conditioned B cells leads to increased production of immunoregulatory cytokines and reduced CNS inflammation, as well as decreased expression of the chemokine receptor, CXCR5, and elevated BDNF expression in the CNS. Thus B cells can protect against EAE, and GA augments this effect in maintaining immune homeostasis and controlling EAE disease progression.

SUMMARYIn order to study the interaction between a g -herpesvirus and malaria we established a co-infection model that involves infection of mice with murine g -herpesvirus (MHV-68) and Plasmodium yoelii nonlethal strain (PYNL). To investigate the interaction between acute malaria and the lytic stage of MHV-68, the timing of infections was chosen such that the peak virus and parasite burdens would be present at the same time. Under this condition, we observed significant mortality in co-infected mice and aggressive lung inflammation with a marked influx of neutrophils and megakaryocytes. If mice were latently infected with MHV-68 and then co-infected with malaria we noticed significantly less viral load and parasitaemia. Using MHC/peptide tetramer staining we found that acute malaria reduces the anti-MHV-68 CD8 + T cell response in the animals that develop severe disease. Our study provides important fundamental information, which will be of use when devising strategies to combat infections with more than one agent, a situation that often occurs naturally.