The Next Linear Collider machine protection system

The Next Linear Collider (NLC) electron and positron beams are capable of damaging the linac accelerating structure and beamline vacuum chambers during an individual aberrant accelerator pulse. Machine protection system (MPS) considerations, outlined in this paper, have an impact on the engineering and design of most machine components downstream of the damping ring injector complex. The MPS consists of two functional levels. The first is a system that provides a benign, single bunch, low intensity, high emittance beam that will be used for commissioning and at any time that the integrity or the settings of the downstream component are in doubt. This level also provides for the smooth transition back and forth between high power operation and the benign diagnostic pilot bunch operation. The pilot bunch parameters in the main linac are estimated on the basis of the expected stress in the accelerator structure copper. Beam tests have been done at the SLAC linac to examine the behaviour of the copper at the damage stress threshold. Typical pilot beam parameters (compared with nominal) are: 10 times reduced intensity, 10 times increased horizontal emittance and 1000 times increased vertical emittance, resulting in a reduction in charge density of 105. The second level is the primary protection against a single aberrant pulse. It’s goal is to reduce the possibility that a substantial transverse field changes the trajectory of the high power beam from one pulse to the next. All devices that could produce such a field are 1) monitored by a fast response network and 2) have deliberately slowed response times. A ‘maximum allowable interpulse difference ’ is evaluated for each such device as well as the beam trajectory monitors in each interpulse period.

Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost

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

Measurements of longitudinal phase space in the SLC linac

The electron and positron bunch distributions in the Stanford Linear Collider (SLC) linac have been measured using a Hamamatsu, model N3373-02, 500-femtosecond streak camera. The distributions were measured at the end of the SLC linac versus the bunch compressor RF voltage. The energy spread at the end of the linac was also measured using a wire scanner. The effects of the bunch compressor on the shape of the bunch distribution are also presented