Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with either high-dose (100 µg of p PyCSP plus 30 µg of pGM-CSF) or low-dose (1 µg of p PyCSP plus 1 µg of pGM-CSF DNA) priming were protected against challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30 to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector CD8+-T-cell population present 2 weeks after boosting had ex vivo Ag-specific cytolytic activity, expressed both gamma interferon (IFN-{gamma}) and tumor necrosis factor alpha, and constituted 12 to 20% of splenic CD8+ T cells. In contrast, the memory CD8+-Ag-specific-cell population at 28 weeks lacked cytolytic activity and constituted only 6% of splenic CD8+ T cells, but at the single-cell level it produced significantly higher levels of IFN-{gamma} than the effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was similarly immunogenic and as protective as high-dose priming against a 50-, but not a 250-, sporozoite challenge. These results demonstrate that a heterologous priming and boosting vaccination can provide lasting protection against malaria in this model system

Mapping Cosmic Dawn and Reionization: Challenges and Synergies

Cosmic dawn and the Epoch of Reionization (EoR) are among the least explored observational eras in cosmology: a time at which the first galaxies and supermassive black holes formed and reionized the cold, neutral Universe of the post-recombination era. With current instruments, only a handful of the brightest galaxies and quasars from that time are detectable as individual objects, due to their extreme distances. Fortunately, a multitude of multi-wavelength intensity mapping measurements, ranging from the redshifted 21 cm background in the radio to the unresolved X-ray background, contain a plethora of synergistic information about this elusive era. The coming decade will likely see direct detections of inhomogenous reionization with CMB and 21 cm observations, and a slew of other probes covering overlapping areas and complementary physical processes will provide crucial additional information and cross-validation. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis should be a high priority, closely coupled to computational models and theoretical predictions.Comment: 5 pages, 1 figure, submitted to the Astro2020 Decadal Survey Science White Paper cal

Mapping Cosmic Dawn and Reionization: Challenges and Synergies:Astro2020 Science White Paper

Cosmic dawn and the Epoch of Reionization are among the least explored observational eras in cosmology. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis from experiments probing this epoch should be a high priority, closely coupled to the computational models and theoretical predictions. <p/

Mapping Cosmic Dawn and Reionization: Challenges and Synergies:Astro2020 Science White Paper

Cosmic dawn and the Epoch of Reionization are among the least explored observational eras in cosmology. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis from experiments probing this epoch should be a high priority, closely coupled to the computational models and theoretical predictions. <p/

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

Mapping Cosmic Dawn and Reionization: Challenges and Synergies

Cosmic dawn and the Epoch of Reionization (EoR) are among the least explored observational eras in cosmology: a time at which the first galaxies and supermassive black holes formed and reionized the cold, neutral Universe of the post-recombination era. With current instruments, only a handful of the brightest galaxies and quasars from that time are detectable as individual objects, due to their extreme distances. Fortunately, a multitude of multi-wavelength intensity mapping measurements, ranging from the redshifted 21 cm background in the radio to the unresolved X-ray background, contain a plethora of synergistic information about this elusive era. The coming decade will likely see direct detections of inhomogenous reionization with CMB and 21 cm observations, and a slew of other probes covering overlapping areas and complementary physical processes will provide crucial additional information and cross-validation. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis should be a high priority, closely coupled to computational models and theoretical predictions