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Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi. Currently there are about 8 million infected people worldwide, most of them at the chronic phase of the disease, which involves cardiac, digestive or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective at the initial phase of the infection, which is generally underdiagnosed. Selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in the vertebrate host. Here we report the effectiveness of the vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of chronic tissue parasitism, and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression as well as a second challenge with T. cruzi. Interestingly, inoculation with wild type baculovirus trained the immune system to partially protect mice against T. cruzi. In brief, we demonstrated, for the first time, that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, being a promising vaccine for Chagas’ disease.

Introduction Granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein produced in the lung, is essential for pulmonary host defense and alveolar integrity. Prior studies suggest potential benefits in several pulmonary conditions, including acute respiratory distress syndrome and viral infections. This trial evaluated the effect of the addition of inhaled sargramostim (yeast-derived, glycosylated recombinant human GM-CSF) to standard of care (SOC) on oxygenation and clinical outcomes in patients with COVID-19-associated acute hypoxemia. Materials and Methods A randomized, controlled, open-label trial of hospitalized adults with COVID-19-associated hypoxemia (oxygen saturation Results In total, 122 patients were treated (sargramostim, n = 78; SOC, n = 44). The sargramostim arm experienced greater improvement in P(A–a)O2 by day 6 compared to SOC alone (least squares [LS] mean change from baseline [SE]: −102.3 [19.4] versus −30.5 [26.9] mmHg; LS mean difference: −71.7 [SE 33.2, 95% CI −137.7 to −5.8]; P = .033; n = 96). By day 14, 11.5% (9/78) of sargramostim and 15.9% (7/44) of SOC arms required intubation (P = .49). The 28-day mortality was 11.5% (9/78) and 13.6% (6/44) in the sargramostim and SOC arms, respectively (hazard ratio 0.85; P = .76). Treatment-emergent adverse events occurred in 67.9% (53/78) and 70.5% (31/44) on the sargramostim and SOC arms, respectively. Conclusions The addition of inhaled sargramostim to SOC improved P(A–a)O2, a measure of oxygenation, by day 6 in hospitalized patients with COVID-19-associated acute hypoxemia and was well tolerated. Inhaled sargramostim is delivered directly to the lung, minimizing systemic effects, and is simple to administer making it a feasible treatment option in patients in settings where other therapy routes may be difficult. Although proportionally lower rates of intubation and mortality were observed in sargramostim-treated patients, this study was insufficiently powered to demonstrate significant changes in these outcomes. However, the significant improvement in gas exchange with sargramostim shows this inhalational treatment enhances pulmonary efficiency in this severe respiratory illness. These data provide strong support for further evaluation of sargramostim in high-risk patients with COVID-19.