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Zn–air batteries (ZABs) are a promising technology; however, their commercialization is limited by challenges, including those occurring in the electrolyte, and thus, gel polymer electrolytes (GPEs) and hydrogels have emerged as substitutes for traditional aqueous electrolytes. In this work, PVA/PAA membranes were synthesized by the solvent casting method and soaked in 6 M KOH to act as GPEs. The thickness of the membrane was modified (50, 100, and 150 μm), and after determining the best thickness, the membrane was modified with synthesized SiO2 nanospheres and multi-walled carbon nanotubes (CNTs). SEM micrographs revealed that the CNTs displayed lengths of tens of micrometers, having a narrow diameter (95 ± 7 nm). In addition, SEM revealed that the SiO2 nanospheres had homogeneous shapes with sizes of 110 ± 10 nm. Physicochemical experiments revealed that SiO2 incorporation at 5 wt.% increased the water uptake of the PVA/PAA membrane from 465% to 525% and the ionic conductivity to 170 mS cm−1. The further addition of 0.5 wt.% CNTs did not impact the water uptake but it promoted a porous structure, increasing the power density and the stability, showing three-times-higher rechargeability than the ZAB operated with the PVA/PAA GPE.

En este trabajo se combinan un modelo de línea de espera y un modelo insumo producto. El objetivo es evaluar el impacto económico en cada entidad fronteriza mexicana del norte debido a un impulso de una reducción de 10 minutos del tiempo de espera en el sistema aduanal para el transporte de carga. Lo anterior debido a que el congestionamiento vial de vehículos comerciales con mercancías de exportación en los puertos de cruces fronterizos es un problema crítico para la competitividad e integración económica de México y Estados Unidos. Los resultados muestran que la Producción Bruta Total aumenta 1.6% en Baja California, 1.2% en Sonora, 1.5% en Chihuahua, 1.1% en Coahuila, 0.7% en Nuevo León y 1.8% en Tamaulipas.

Zn–Mn alloy coatings with small amounts of Mn (Zn-0.19 wt.% Mn, Zn-0.21 wt.% Mn, Zn-0.26 wt.% Mn and Zn-0.34 wt.% Mn) were formed by electrodeposition, onto pre-treated Mg substrates (Mgt) covered with a Zn film (Zn/Mgt). The chemical composition in depth profiles, morphological and structural characteristics of the Zn–Mn coatings on Zn/Mgt (labeled as Zn–Mn/(Zn/Mgt)) were analyzed using Glow Discharge Optical Emission Spectroscopy (GD-OES), Scanning Electron Microscopy/Energy Dispersive X-ray spectroscopy (SEM/EDS), and X-ray diffraction (XRD). When the manganese content was greater than 0.19 wt.%, the results reveal the formation of two Zn–Mn phases: η-ZnMn and ζ-MnZn13; while the formation of the ζ-MnZn13 phase was favored by increasing the Mn content in the alloy. On the other hand, microhardness, wear resistance, and coefficient of friction significantly increase when coating Zn/Mgt substrate with the Zn–Mn alloy. The corrosion performance of this alloy was evaluated by potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS). The degradation rate in Hank's solutions of the pristine Mg substrate (0.29 mm yr−1) decreases due to the Zn–Mn coating. Furthermore, the degradation rate of Zn–Mn was further decreased from 0.051 to 0.022 mm yr−1, by varying the amount of Mn in the Zn–Mn alloy from 0.19 to 0.26 wt.% Mn, respectively. However, the rate of degradation increases up to 0.064 mm yr−1 at higher Mn content, Zn-0.34 wt.% Mn. Therefore, the microhardness, wear volume, and degradation rate of Zn–Mn/(Zn/Mg) in Hank's solution can be modulated by varying the Mn composition in the alloy.

A raíz de la crisis sanitaria ocasionada por la pandemia de COVID-19, una de las medidas del gobierno federal mexicano fue la suspensión de algunas actividades productivas no esenciales. A partir de ello, el presente trabajo pretende ofrecer un análisis de la afectación que este escenario ha traído para el nivel general de precios, el cual se realiza utilizando el Método de Extracción Hipotética (MEH) aplicado sobre la Matriz de Insumo Producto de México actualizada a 2019, lo cual permite observar, a un nivel desagregado por sectores, el impacto que origina la reducción de los insumos intermedios y de la intensidad del trabajo en las actividades productivas. El resultado de este estudio muestra un efecto deflacionario que es observable en mayor medida en los sectores manufacturero e inmobiliario.

En 2019 el nuevo gobierno federal mexicano decretó un paquete económico que incluye un cambio en la tasa del impuesto al valor agregado (IVA) de 16% a 8% para empresas registradas para facturación en la región fronteriza norte de México (RFN). Para medir cómo se transmite la rebaja impositiva completamente –efectos directos e indirectos— sobre cambios en el nivel general de precios en el corto plazo, así como también su impacto económico sobre la producción bruta, ocupación de personal y valor agregado a corto plazo, empleamos los precios implícitos en la tabla insumo producto estimada para la RFN. Los resultados muestran que el estímulo fiscal –si 100% de las empresas están registradas—: 1) inducirá una caída de – 2.3% en precios generales de la RFN; 2) a su vez, la caída de precios generales provocará un alza en la producción bruta en 2.9%; en la ocupación laboral en 2.2% y en el valor agregado en 2.6% para la RFN; e indican que, 3) la IMMEX es menos sensible en estas variables clave debido a la baja integración de insumos nacionales.

Biopolymers are promising materials as electrolytes with high flexibility, good performance, cost effectiveness, high compatibility with solvents, and film-forming ability. Chitosan (CS) and carboxymethylcellulose (CMC) can form an intermolecular complex, giving rise to hydrogels capable of absorbing ionic solutions. Citric acid (CA) is an effective biological chemical crosslinker that assists the formation of amide and ester bonds between CMC and CS, resulting in a structure with high ionic conductivity and good structural integrity. In this study, a chemical crosslinking strategy is used to synthesize electrolyte hydrogels for zinc–air batteries. The effects of crosslinking are studied on the structural and electrochemical performance of the membranes. The results show an improvement in the ionic conductivity with respect to the homologous electrolyte hydrogel systems reported, with a maximum of 0.19 S∙cm−1 at 30 °C. In addition, the cyclic voltammetry studies showed a current intensity increase at higher CA content, reaching values of 360 mA∙cm−2. Structural characterization suggests a higher thermal stability and a decrease in the degree of crystallinity caused by the polymers’ crosslinking. Finally, these membranes were tested in Zn–air batteries, obtaining power densities of 85 mW∙cm−2. The proposed hydrogels show to be appropriate for energy zinc–air battery applications and present an alternative to support the sustainable energy transition.

El texto analiza del patrón espacio-temporal de propagación del COVID-19 en los municipios de Baja California desde la semana epidemiológica 10 hasta la 31 con base en las metodologías de Dinámica de Sistemas (ds) y Sistemas de Información Geográfica (sig). Se usa el modelo susceptibles, infectados y recuperados (sir) epidémico a fin de modelar los factores críticos de contagio de la pandemia —tasa de infección y tasa de recuperación de la infección— con datos de la Dirección General de Epidemiología de la Secretaría de Salud disponibles el día 6 de junio de 2020. El patrón epidemiológico tiende a concentrase espacialmente en Mexicali, Tijuana y Tecate, ciudades que albergan a los trabajadores transfronterizos entre las Californias. Además, presenta una dinámica temporal cambiante hacia los municipios de Ensenada y Playas de Rosarito que son el destino de mayor demanda de los turistas californianos.

El objetivo del estudio es medir el efecto en la economía de la región fronteriza del incremento del salario mínimo a partir de la declaración de la zona libre de la frontera a principios de 2019. La medición se basa en un enfoque de precios del modelo de insumo-producto siguiendo la propuesta de Park (2006) y en una estimación propia de la matriz de insumo-producto para la región. La evaluación consideró el alza de 100% del salario mínimo que favoreció alrededor de 631 mil de trabajadores ―146 mil de la industria maquiladora y 485 mil en el resto de los sectores―. Los resultados del modelo muestran un incremento de 2.9% sobre la inflación, y asociado a ello se espera un ajuste a la baja de la producción de 1%, del personal ocupado de 1.7% y del valor agregado de 1.1%. En particular, la industria maquiladora es menos sensible a estas variables clave, ya que el salario medio pagado por ellas era más cercano al salario mínimo establecido. Adicionalmente, hay un impacto positivo en el ingreso de los trabajadores de salario mínimo en la industria maquiladora, pues ahora ganan 6.8% más, y del resto de los sectores, ya que ahora ganan 9.7% más. Si se toma en cuenta lo anterior, se puede establecer que la política laboral regional es una medida de bajos efectos inflacionarios y de contracción, aunque ligera, en la actividad económica, pero que mejora el poder adquisitivo de los que menos ganan.

Según estadísticas tradicionales de comercio exterior, el TLCAN ha sido consistente con una balanza comercial superavitaria para México con respecto a EE. UU. Sin embargo, usando una tabla insumo-producto bilateral que permite computar el valor agregado, y no el valor bruto de las exportaciones, se modifica el saldo entre estos dos socios comerciales. El flujo de valor agregado en las exportaciones de México a EE. UU. alcanza los 164.4 millardos de dólares, 4 mientras que el contenido de EE. UU. a México es de 188.7 millardos de dólares. En la desagregación del valor agregado contenido en las exportaciones destaca la gran diferencia entre los componentes doméstico y extranjero, pues mientras que para EE. UU. el componente extranjero alcanza los 2.5 millardos, para México es de 50.2 millardos de dólares, que es más de 20 veces el monto que representa el mismo para los EE. UU. Una conclusión que se deriva directamente de este último aspecto es que durante el TLCAN una parte importante de los ingresos por exportaciones mexicanas se destinó a remunerar factores productivos empleados en los EE. UU. Otra es que cualquier modificación del TLCAN que imponga un aumento del contenido extranjero a México, implicará un menor ingreso de divisas netas por cada dólar exportado. Consecuentemente, el comercio exterior tendrá un menor efecto multiplicador sobre la actividad doméstica mexicana debido que el mayor impulso de las exportaciones bilaterales recaerá indirectamente en EE. UU.

El objetivo del texto es simular el modelo insumo producto dinámico adaptado por Johnson (1986) combinando el enfoque insumo producto con la metodología de simulación dinámica de sistemas para el análisis del sistema ecológico-económico. Para la simulación del modelo empleamos el software Stella que permite realizar una programación por objetos muy sencilla, versátil e intuitiva. Como ilustración de la utilidad de la simulación del modelo calculamos los multiplicadores de producción dinámicos para la economía de Coahuila en ciertos años seleccionados entre 2015 y 2035. Las autoridades estatales están interesadas en conocer cómo un conjunto de políticas diseñadas para reducir las emisiones totales de gas efecto invernadero (GEI) afectan el volumen de producción local. Desde el punto de vista de la planeación ambiental local es muy útil saber la magnitud, la composición sectorial y tiempos de ocurrencia de tales impactos de política medioambiental.

El uso de las tecnologías de la información y la comunicación hoy en el presente ha llegado a ser uno de los pilares básicos de la sociedad, igual que su influencia en los procesos educativos, teniendo en cuenta las posibilidades educativas, para promover el aprender y el enseñar, es decir el aprendizaje de cualquier materia o habilidad que se puede facilitar tanto para el docente como el estudiante en la ardua búsqueda del conocimiento. Este artículo se centrara en tecnologías informáticas para la educación, ya que las persona encargadas de la enseñanza buscan desarrollar procesos y herramientas afines para la de generación de conocimiento, que son impactadas por el desarrollo de las TIC. Así poder difundir el conocimiento de manera colaborativa para los educadores que hacen parte de la comunidad de los LMS.

El principal propósito del estudio es presentar una estrategia metodológica que analiza los impactos económicos del Sistema de Protección Social en Salud (SPSS) en el estado de Tabasco, a través de la vinculación de la Cuenta Satélite en Salud y la Matriz Insumo Producto del estado. Así, el objetivo general del análisis consiste en valorar el alcance de los impactos, es decir, definir su intensidad según su efecto sobre los indicadores de ingreso, producción y empleo en el estado.

El análisis estructural de la economía de Baja California, desde la teoría de redes, parte de la aplicación de una técnica innovadora con enfoque cuantitativo, cuya aportación permite resaltar los rasgos más sobresalientes de una red productiva, de forma coherente y simplificada; además, sus características particulares e incorporación al análisis económico suponen un reto al estudio de la estructura productiva a escala regional o nacional.

Las remesas familiares que envían los migrantes mexicanos en EUA son relevantes para las familias receptoras en al menos dos sentidos: contribuyen a elevar el ingreso y en consecuencia, a disminuir los niveles de pobreza y, mediante los multiplicadores que generan con el aumento de la demanda y de la inversión en actividades productivas, también contribuyen al desarrollo económico local y regional. No obstante, existen diversas estimaciones sobre la magnitud de las remesas familiares. Este documento analiza las metodologías oficial del Banco de México y las propuestas de reconocidos investigadores. No existe consenso acerca del volumen del dinero transferido por los migrantes mexicanos en los EUA. En consecuencia, los efectos positivos en la economía receptora pueden no ser concluyentes.

Based on a multisectors approach, this document set upaggregated restricted social accounting matrix of 10villages in Mexico. This paper, analyze the effects of anexogenous increase in the product equivalent to 100 pesosper capita onto the rural households’ income and reducingpoverty. Furthermore migration and the salaried work therural households perform five productivity activities:commercial agriculture, livestock, staple crops, forestry andfirewood gathering, and commerce and services. On thebasis of three simulations we are to obtain that the impacton the income and reduction of poverty of the ruralhouseholds of an external injection depends of the activityto which it is applied; the dimension of the accountingmultipliers depends on the participation and of the linkagesof each activity on the local and external economy. The results show that the commerce and services (1.75 to 2.28), staple crops (1.36 to 2.21), and livestock (1.36 to 1.84)present the largest multiplier effects.

Se utiliza el modelo de insumo-producto para analizar la importancia de la administración pública en el D.F. respecto del ámbito nacional. A diferencia del enfoque tradicional, el enfoque adoptado introduce una división tecnológico-institucional que muestra por separado la participación del sector privado y público en la formación y uso de la producción. Se crea una actividad en el modelo de interdependencias que se denomina sector gobierno o administración pública, que incluye las relaciones de regulación y los servicios generales de gobierno que originan corrientes de insumos intermedios, factores, producción y valor agregado. Del análisis de la descomposición sectorial se muestra que el comportamiento sectorial diferenciado del valor de la producción bruta y valor agregado censal bruto entre el D.F. y la nación se fundamenta en el componente de demanda final interna más que en el componente tecnológico.

En este estudio se aplica la teoría de grafos para realizar un análisis estructural de la economía mexicana; la fuente de información es la matriz de transacciones intersectoriales de la tabla nacional de insumo-producto, 2003 (INEGI, 2008). El grafo de influencia relativa asociado a la tabla nacional permite analizar las relaciones de dominación-dependencia entre los diferentes sectores productivos en su doble vertiente de compradores y vendedores, lo que también brinda una visión estructural del comportamiento del conjunto de tales relaciones. El método permite realizar una jerarquización sectorial que tiene en cuenta las relaciones globales de dependencia; se basa en unas medidas relativas de atracción que, al hacer abstracción del peso individual de cada sector de la economía, proporcionan una visión más real de la estructura de las relaciones intersectoriales. Cabe destacar que éste es un aspecto no incorporado en el análisis estructural clásico de insumo-producto.

Este artículo investiga la estructura de encadenamientos hacia atrás en la economía de Baja California, mediante un conjunto de técnicas para identificar sectores clave en un modelo de insumoproducto (MIP) abierto y cerrado. En particular, el estudio se centra en el análisis de la relación tanto entre la incorporación de insumos nacionales y la promoción de la industria maquiladora de exportación (IME), como entre el crecimiento económico regional y encadenamientos hacia atrás.

El objetivo de este trabajo es analizar la evolución de las disparidades municipales del producto bruto por habitante con un conjunto de medidas utilizadas en el estudio de la distribución personal del ingreso y complementado con la técnica de la regresión cuantílica. Del análisis inferimos que las disparidades regionales caracterizan cada vez más la agenda económica, social y política de México. La atención puesta en la descentralización y el crecimiento económico, mediante el control riguroso del gasto público social, provocaron un aumento en la privatización de servicios públicos básicos, un mayor conflicto en el ámbito subnacional y la intensificación de las disparidades regionales. El auténtico avance hacia la reducción de las disparidades regionales exige la unidad de propósitos federal-estatal-municipal. El gobierno federal de minoría enfrenta la decisión de generar la cooperación intergubernamental o una mayor balcanización espacial.

Objetivo. Analizar las políticas públicas formuladas para tratar el consumo de drogas en menores de edad de la ciudad de Manizales con el fin de examinar su incidencia en el incremento del consumo por parte de esta población. Metodología. Se hace uso de una metódica mixta, que permite relacionar estratégicamente datos cuantitativos con datos cualitativos. Resultados. Se propone la construcción de una política social a partir de un modelo alternativo enfocado en una gobernanza equilibrada y horizontal que permita a la sociedad civil involucrarse en la toma de decisiones para su formulación e implementación local. Conclusiones. Estas políticas públicas no son efectivas, ya que expresan cierta incertidumbre jurídica que simultáneamente prohíbe y permite el consumo de drogas.

Este trabajo presenta un modelo de insumo-producto, que intenta analizar el papel del sector energético en la economía del estado de Nuevo León. El objetivo es cuantificar el efecto derrame causado en la entidad por el impacto negativo que puede provocar la elevación de precios de los derivados petrolíferos, gas natura l y electricidad en ciertos sectores productivos. El aumento exógeno en los precios de los productos energéticos atenta contra la continuidad del proceso de crecimiento económico de Nuevo León, puesto que el estado tiene un perfil energético cuya tasa de consumo es superior al promedio nacional, y el desarrollo económico e industrial se ha traducido inevitablemente en un aumento del consumo de ellos.

En el trabajo se estima la matriz insumo-producto para el estado de Baja California desde el enfoque indirecto conocido como partial survey method, que se basa en el procedimiento tipo RAS, pero ajustado al espacio y a la información exógenas disponible de las transacciones intersectoriales. Los objetivos para estimar dicha matriz regional son dos: a) detallar el proceso de generación de datos regionales y, b) promover la participación activa de los interesados en la discusión del análisis regional. La principal ventaja del procedimiento RAS es su relativa simplicidad y confiabilidad; sin embargo, su desventaja es la imposibilidad de ajustar los coeficientes nulos, lo cual implica que los coeficientes técnicos de producción permanezcan constantes.

Por medio del análisis de re g resión se calcula para México una función de cuasi-pro d u c c i ó n , a fin de examinar si la inversión pública en infraestructura puede alterar los pat rones de ingreso re g i o n a l , así como para determinar si la efectividad de dicho tipo de inversión depende de su composición (económica y social) y de las características de las regiones re c e p t o r a s ( i n t e rmedias o re z ag a d a s ) .Hansen (1965) ha señalado esta posibilidad. Las entidades federativas fueron agrupadas mediante clusters y discriminantes en dos categorías: intermedias y rezagadas. Los resultados econométricos parecen confirmar la tesis de Hansen. Cada indicador físico (sintético) de inversión pública económica fue estadísticamente significativo para e xplicar las va riaciones regionales del P I B E ( p ro d u c t o i n t e rno bruto estatal) en la categoría de estados int e rm e d i o s. Si bien el indicador físico (sintético)de infraestructura social resultó estadísticamente significativo en la explicación de las dife rencias del P I B E p e r c a p i t a en la categoría de estados at r a s a d o s , no lo fue en la categoría de estados intermedios. En otras palabras, el análisis empírico realizado pone en evidencia que la e fectividad de la inversión pública en infraestructura depende de su composición y de las características de las regiones receptoras.

El objetivo de este trabajo es analizar si los factores que condicionan la convergencia β-condicional, varían su influencia según el nivel de desarrollo económico de las regiones. Con un total de 2, 443 municipios, para los años 1989, 1995, 2000 y 2004, se realizaron estimaciones mediante regresiones cuantílicas con la tasa de crecimiento del ingreso por habitante, como variable dependiente; y, el nivel inicial de ingreso por habitante, infraestructura urbana básica (agua, drenaje, electricidad) y educación, como variables independientes. Los resultados muestran que la regresión cuantílica proporciona una perspectiva más completa de los determinantes de la convergencia económica que la regresión MCO estándar. La convergencia se ve condicionada por un comportamiento jerárquico, debido probablemente a la mayor flexibilidad de los municipios ricos para aprovechar las opciones propias y del entorno. Se constata que las variables de infraestructura básica se vuelven más grandes y significativas mientras más rico es el municipio, en tanto que el impacto de la educación parece ser similar entre los municipios ricos y pobres.

Este artículo desarrolla un marco de trabajo consistente para identificar sectores clave o estratégicos, y para evaluar la importancia regional de sectores individuales de acuerdo a diferentes indicadores, usando tablas regionales de recursos y producción. La metodología se aplica al caso de Baja California Sur, México, en la discusión actual acerca de una posible nueva estrategia de desarrollo económico. Se tomó en cuenta tanto la perspectiva política como la estructura tecnológica. Los resultados confirman la existencia de sectores líderes o tradicionales que se consideran estratégicos o claves. Tales sectores se caracterizan por tener muy débiles vínculos sectoriales con el resto de las actividades económicas y por no ejercer una influencia significativa sobre la producción de otros sectores y, con ello, sobre el mercado de trabajo regional. Las conclusiones confirman la urgencia de revisar los planes para el desarrollo económico de la región, para así poder incluir consideraciones de corto y largo alcance, así como la perspectiva cuantitativa que las apoye y refuerce

La matriz de insumo-producto es una herramienta muy versátil debido a que nos permite examinar los encadenamientos entre los sectores. También la tabla de insumo-producto puede ser utilizada para describir la economía regional o realizar análisis y pronósticos relacionados con ésta. En este artículo mostramos cómo la tabla de insumo-producto puede contribuir al entendimiento de las articulaciones interindustriales y la estructura económica de Mexicali. Asimismo aplicamos el modelo para comprender las fuentes del crecimiento económico municipal: cuáles grupos tienen más probabilidades de beneficiarse con éste y cuáles no las tienen o pueden ser perjudicados por este desarrollo.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria., Competing Interests: Declaration of interests J.R.B., A.J.R.C., G.G., B.G.W., L.D.W.K., L.T.W., J.T., K. McHugh, and S.J.D. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. A.M.M. and S.J.D. have consulted to GSK on malaria vaccines. A.M.M. has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials., Competing Interests: Declaration of interests S.J.D. is an inventor on patent applications relating to RH5 malaria vaccines and antibodies, is a co-founder of and shareholder in SpyBiotech, and has been a consultant to GSK on malaria vaccines. A.M.M. has been a consultant to GSK on malaria vaccines, has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies, and is a co-founder of and shareholder in SpyBiotech. M.R.H. is an inventor on patents relating to peptide targeting via spontaneous amide bond formation and is a co-founder of and shareholder in SpyBiotech. S.B. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and is a co-founder of, shareholder in, and employee of SpyBiotech. J.J. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and is a co-founder of and shareholder in SpyBiotech. R.A.D. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and shareholder in SpyBiotech. L.D.W.K., J.R.B., D.Q., A.M.L., S.E.S., B.G.W., K. McHugh, I.C., S.J.F., and D.P. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial., (© 2024. The Author(s).)

Background: RH5 is the leading vaccine candidate for the Plasmodium falciparum blood stage and has shown impact on parasite growth in the blood in a human clinical trial. RH5 binds to Ripr and CyRPA at the apical end of the invasive merozoite form, and this complex, designated RCR, is essential for entry into human erythrocytes. RH5 has advanced to human clinical trials, and the impact on parasite growth in the blood was encouraging but modest. This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr and CyRPA to provide improved neutralizing activity against P. falciparum in vitro., Methods: Mice were immunized with the individual RCR antigens to down select the best performing adjuvant formulation and rats were immunized with the individual RCR antigens to select the correct antigen dose. A second cohort of rats were immunized with single, double and triple antigen combinations to assess immunogenicity and parasite neutralizing activity in growth inhibition assays., Results: The DPX® platform was identified as the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. The three antigens derived from RH5, Ripr and CyRPA proteins formulated with DPX induced highly inhibitory parasite neutralising antibodies. Notably, RH5 either as a single antigen or in combination with Ripr and/or CyRPA, induced inhibitory antibodies that outperformed CyRPA, Ripr., Conclusion: An RCR combination vaccine may not induce substantially improved protective immunity as compared with RH5 as a single immunogen in a clinical setting and leaves the development pathway open for other antigens to be combined with RH5 as a next generation malaria vaccine., Competing Interests: The authors LL and RR are employed, and MS was employed by IMV Inc. JC, AN and VK are employed by Leidos Life Sciences. SD is a named inventor on patent applications relating to RH5-based malaria vaccines. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Healer, Thompson, Mackwell, Browne, Seager, Ngo, Lowes, Silk, Pulido, King, Christen, Noe, Kotraiah, Masendycz, Rajagopalan, Lucas, Stanford, Soisson, Diggs, Miller, Youll, Wycherley, Draper and Cowman.)

The hurdles to effective blood stage malaria vaccine design include immune evasion tactics used by the parasite such as redundant invasion pathways and antigen variation among circulating parasite strains. While blood stage malaria vaccine development primarily focuses on eliciting optimal humoral responses capable of blocking erythrocyte invasion, clinically-tested Plasmodium falciparum (Pf) vaccines have not elicited sterile protection, in part due to the dramatically high levels of antibody needed. Recent development efforts with non-redundant, conserved blood stage antigens suggest both high antibody titer and rapid antibody binding kinetics are important efficacy factors. Based on the central role of helper CD4 T cells in development of strong, protective immune responses, we systematically analyzed the class II epitope content in five leading Pf blood stage antigens (RH5, CyRPA, RIPR, AMA1 and EBA175) using in silico , in vitro , and ex vivo methodologies. We employed in silico T cell epitope analysis to enable identification of 67 HLA-restricted class II epitope clusters predicted to bind a panel of nine HLA-DRB1 alleles. We assessed a subset of these for HLA-DRB1 allele binding in vitro , to verify the in silico predictions. All clusters assessed (40 clusters represented by 46 peptides) bound at least two HLA-DR alleles in vitro . The overall epitope prediction to in vitro HLA-DRB1 allele binding accuracy was 71%. Utilizing the set of RH5 class II epitope clusters (10 clusters represented by 12 peptides), we assessed stimulation of T cells collected from HLA-matched RH5 vaccinees using an IFN-γ T cell recall assay. All clusters demonstrated positive recall responses, with the highest responses - by percentage of responders and response magnitude - associated with clusters located in the N-terminal region of RH5. Finally, a statistically significant correlation between in silico epitope predictions and ex vivo IFN-γ recall response was found when accounting for HLA-DR matches between the epitope predictions and donor HLA phenotypes. This is the first comprehensive analysis of class II epitope content in RH5, CyRPA, RIPR, AMA1 and EBA175 accompanied by in vitro HLA binding validation for all five proteins and ex vivo T cell response confirmation for RH5., Competing Interests: AN, TP, KT, VK, and GG are employees of Leidos, Inc., the prime contractor for the USAID Malaria Vaccine Development Program (MVDP) Contract AID-OAA-C-15-00071. FT, PH, LM, WM, and ADG are employees of EpiVax, Inc., an MVDP subcontractor. PH is a previous employee of EpiVax, Inc. SD, SS, CN, and RA are employees of the University of Oxford, an MVDP subcontractor. SD is a named inventor on patent applications relating to the RH5-based vaccines used in the VAC057 and VAC063 clinical studies., (Copyright © 2021 Kotraiah, Phares, Terry, Hindocha, Silk, Nielsen, Moise, Tucker, Ashfield, Martin, De Groot, Draper, Gutierrez and Noe.)

Background: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Plasmodium falciparum ., Methods: We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the P. falciparum reticulocyte-binding protein homolog 5 (RH5), formulated in AS01 B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145., Findings: The RH5.1/AS01 B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 μg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Following primary and secondary CHMI of vaccinees with blood-stage P. falciparum , a significant reduction in parasite growth rate was observed, defining a milestone for the blood-stage malaria vaccine field. We show that growth inhibition activity measured in vitro using purified immunoglobulin G (IgG) antibody strongly correlates with in vivo reduction of the parasite growth rate and also identify other antibody feature sets by systems serology, including the plasma anti-RH5 IgA1 response, that are associated with challenge outcome., Conclusions: Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease., Funding: This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC., Competing Interests: A.D.D. and S.J.D. are named inventors on patent applications relating to RH5 and/or other malaria vaccines and immunization regimens. W.A.d.J. is an employee of and shareholder in ExpreS2ion Biotechnologies, which has developed and is marketing the ExpreS2 cell expression platform. A.R.N. is an employee of Leidos, Inc., which holds the MVDP prime contract (AID-OAA-C-15-00071). A.M.M. has an immediate family member who is an inventor on patents relating to RH5 and/or other malaria vaccines and immunization regimens., (© 2021 The Author(s).)

An effective malaria vaccine must prevent disease in a range of populations living in regions with vastly different transmission rates and protect against genetically-diverse Plasmodium falciparum (Pf) strains. The protective efficacy afforded by the currently licensed malaria vaccine, Mosquirix™, promotes strong humoral responses to Pf circumsporozoite protein (CSP) 3D7 but protection is limited in duration and by strain variation. Helper CD4 T cells are central to development of protective immune responses, playing roles in B cell activation and maturation processes, cytokine production, and stimulation of effector T cells. Therefore, we took advantage of recent in silico modeling advances to predict and analyze human leukocyte antigen (HLA)-restricted class II epitopes from PfCSP - across the entire PfCSP 3D7 sequence as well as in 539 PfCSP sequence variants - with the goal of improving PfCSP-based malaria vaccines. Specifically, we developed a systematic workflow to identify peptide sequences capable of binding HLA-DR in a context relevant to achieving broad human population coverage utilizing cognate T cell help and with limited T regulatory cell activation triggers. Through this workflow, we identified seven predicted class II epitope clusters in the N- and C-terminal regions of PfCSP 3D7 and an additional eight clusters through comparative analysis of 539 PfCSP sequence variants. A subset of these predicted class II epitope clusters was synthesized as peptides and assessed for HLA-DR binding in vitro . Further, we characterized the functional capacity of these peptides to prime and activate human peripheral blood mononuclear cells (PBMCs), by monitoring cytokine response profiles using MIMIC ® technology (Modular IMmune In vitro Construct). Utilizing this decision framework, we found sufficient differential cellular activation and cytokine profiles among HLA-DR-matched PBMC donors to downselect class II epitope clusters for inclusion in a vaccine targeting PfCSP. Importantly, the downselected clusters are not highly conserved across PfCSP variants but rather, they overlap a hypervariable region (TH2R) in the C-terminus of the protein. We recommend assessing these class II epitope clusters within the context of a PfCSP vaccine, employing a test system capable of measuring immunogenicity across a broad set of HLA-DR alleles., Competing Interests: AN, TP, KT, VK, JC, and GG are employees of Leidos, Inc., prime contractor for USAID Malaria Vaccine Development Program (MVDP) Contract AID-OAA-C-15-00071, and hold Leidos stock and/or stock options. FT, LM, WM, and ADG are employees of EpiVax, Inc., an MVDP subcontractor. PH was a previous employee of EpiVax, Inc. BS, ES, and DD are employees of Sanofi Pasteur, an MVDP subcontractor, and hold Sanofi Pasteur stock and/or stock options., (Copyright © 2021 Noe, Terry, Schanen, Sassano, Hindocha, Phares, Moise, Christen, Tucker, Kotraiah, Drake, Martin, De Groot and Gutierrez.)

Immunization with radiation-attenuated sporozoites (RAS) has been shown to protect against malaria infection, primarily through CD8 T cell responses, but protection is limited based on parasite strain. Therefore, while CD8 T cells are an ideal effector population target for liver stage malaria vaccine development strategies, such strategies must incorporate conserved epitopes that cover a large range of class I human leukocyte antigen (HLA) supertypes to elicit cross-strain immunity across the target population. This approach requires identifying and characterizing a wide range of CD8 T cell epitopes for incorporation into a vaccine such that coverage across a large range of class I HLA alleles is attained. Accordingly, we devised an experimental framework to identify CD8 T cell epitopes from novel and minimally characterized antigens found at the pre-erythrocytic stage of parasite development. Through in silico analysis we selected conserved P. falciparum proteins, using P. vivax orthologues to establish stringent conservation parameters, predicted to have a high number of T cell epitopes across a set of six class I HLA alleles representative of major supertypes. Using the decision framework, five proteins were selected based on the density and number of predicted epitopes. Selected epitopes were synthesized as peptides and evaluated for binding to the class I HLA alleles in vitro to verify in silico binding predictions, and subsequently for stimulation of human T cells using the Modular IMmune In-vitro Construct (MIMIC ® ) technology to verify immunogenicity. By combining the in silico tools with the ex vivo high throughput MIMIC platform, we identified 15 novel CD8 T cell epitopes capable of stimulating an immune response in alleles across the class I HLA panel. We recommend these epitopes should be evaluated in appropriate in vivo humanized immune system models to determine their protective efficacy for potential inclusion in future vaccines., Competing Interests: AN, TP, KT, VK, and GG are employees of Leidos, Inc., the prime contractor for Malaria Vaccine Development Program (MVDP) Contract AID-OAA-C-15-00071. FT, LM, WM, and AG are employees of EpiVax, Inc., an MVDP subcontractor. BS, ES, and DD are employees of Sanofi Pasteur, an MVDP subcontractor. BS, DD, and ES hold Sanofi shares and/or stock options. PH was a previous employee of EpiVax, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tucker, Schanen, Phares, Sassano, Terry, Hindocha, Moise, Kotraiah, Martin, De Groot, Drake, Gutierrez and Noe.)

The blockade of programmed cell death-1 (PD1) and its ligand PDL1 has been proven to be a successful immunotherapy against several cancers. Similar to cancer, PD1 contributes to the establishment of several chronic infectious diseases, including malaria. While monoclonal antibodies (mAbs) targeting checkpoint receptors are revolutionary in cancer treatment, the immune-related adverse events (irAEs) may prevent their utilization in prophylactic and therapeutic treatments of infectious diseases. The irAEs are, in part, due to the prolonged half-life of mAbs resulting in prolonged activation of the immune system. As an alternative modality to mAbs, peptides represent a viable option because they possess a shorter pharmacokinetic half-life and offer more formulation and delivery options. Here, we report on a 22-amino acid immunomodulatory peptide, LD01, derived from a Bacillus bacteria. When combined prophylactically with an adenovirus-based or irradiated sporozoite-based malaria vaccine, LD01 significantly enhanced antigen-specific CD8 + T cell expansion. Therapeutically, LD01 treatment of mice infected with a lethal malaria strain resulted in survival that was associated with lower numbers of FOXP3 + Tbet + CD4 + regulatory T cells. Taken together, our results demonstrate that LD01 is a potent immunomodulator that acts upon the adaptive immune system to stimulate T cell responses both prophylactically and therapeutically., (Copyright © 2020 Phares, Kotraiah, Karunarathne, Huang, Browne, Buontempo, Mansour, Noe, Wykes, Pannucci, Tsuji and Gutierrez.)

Computational vaccinology includes epitope mapping, antigen selection, and immunogen design using computational tools. Tools that facilitate the in silico prediction of immune response to biothreats, emerging infectious diseases, and cancers can accelerate the design of novel and next generation vaccines and their delivery to the clinic. Over the past 20 years, vaccinologists, bioinformatics experts, and advanced programmers based in Providence, Rhode Island, USA have advanced the development of an integrated toolkit for vaccine design called iVAX, that is secure and user-accessible by internet. This integrated set of immunoinformatic tools comprises algorithms for scoring and triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, re-engineering or eliminating regulatory T cell epitopes, and re-designing antigens to induce immunogenicity and protection against disease for humans and livestock. Commercial and academic applications of iVAX have included identifying immunogenic T cell epitopes in the development of a T-cell based human multi-epitope Q fever vaccine, designing novel influenza vaccines, identifying cross-conserved T cell epitopes for a malaria vaccine, and analyzing immune responses in clinical vaccine studies. Animal vaccine applications to date have included viral infections of pigs such as swine influenza A, PCV2, and African Swine Fever. "Rapid-Fire" applications for biodefense have included a demonstration project for Lassa Fever and Q fever. As recent infectious disease outbreaks underscore the significance of vaccine-driven preparedness, the integrated set of tools available on the iVAX toolkit stand ready to help vaccine developers deliver genome-derived, epitope-driven vaccines., (Copyright © 2020 De Groot, Moise, Terry, Gutierrez, Hindocha, Richard, Hoft, Ross, Noe, Takahashi, Kotraiah, Silk, Nielsen, Minassian, Ashfield, Ardito, Draper and Martin.)

Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T cells. Monoclonal antibody (mAb)-based inhibitors to checkpoint receptors have also been shown to enhance T-cell responses in models of chronic infection. Therefore, inhibitors have the potential to act as a vaccine "adjuvant" by facilitating the expansion of vaccine antigen-specific T-cell repertoires. Here, we report the discovery and characterization of a peptide-based class of PD1 checkpoint inhibitors, which have a potent adaptive immunity adjuvant capability for vaccines against infectious diseases. Briefly, after identifying peptides that bind to the recombinant human PD1, we screened for in vitro efficacy in reporter assays and human peripheral blood mononuclear cells (PBMC) readouts. We first found the baseline in vivo performance of the peptides in a standard mouse oncology model that demonstrated equivalent efficacy compared to mAbs against the PD1 checkpoint. Subsequently, two strategies were used to demonstrate the utility of our peptides in infectious disease indications: (1) as a therapeutic in a bacteria-induced lethal sepsis model in which our peptides were found to increase survival with enhanced bacterial clearance and increased macrophage function; and (2) as an adjuvant in combination with a prophylactic malaria vaccine in which our peptides increased T-cell immunogenicity and the protective efficacy of the vaccine. Therefore, our peptides are promising as both a therapeutic agent and a vaccine adjuvant for infectious disease with a potentially safer and more cost-effective target product profile compared to mAbs. These findings are essential for deploying a new immunomodulatory regimen in infectious disease primary and clinical care settings., (Copyright © 2020 Kotraiah, Phares, Browne, Pannucci, Mansour, Noe, Tucker, Christen, Reed, MacKay, Weir, Rajagopalan, Stanford, Chung, Ayala, Huang, Tsuji and Gutierrez.)

Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission., (Copyright © 2017 Espinosa et al.)

An active and tetrameric form of recombinant butyrylcholinesterase (BChE), a large and complex human enzyme, was produced via semicontinuous operation in a transgenic rice cell suspension culture. After transformation of rice callus and screening of transformants, the cultures were scaled up from culture flask to a lab scale bioreactor. The bioreactor was operated through two phases each of growth and expression. The cells were able to produce BChE during both expression phases, with a maximum yield of 1.6 mg BChE/L of culture during the second expression phase. Cells successfully regrew during a 5-day growth phase. A combination of activity assays and Western blot analysis indicated production of an active and fully assembled tetramer of BChE.

In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Studies in animals and human volunteers demonstrate that antibodies against the repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate sporozoite infection. However, the realization that the N- and C- terminal regions flanking the repeats play essential roles in parasite infectivity raised the possibility that they could be targeted by protective antibodies. We characterized a monoclonal antibody (mAb5D5) specific for the N-terminus of the P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5 strongly inhibits the in vivo infection of sporozoites expressing the N-terminus of P. falciparum CSP, and this protection is greatly enhanced when combined with antirepeat antibodies. Our results show that antibodies interfering with molecular processes required for parasite infectivity can exert a strong in vivo protective activity and indicate that pre-erythrocytic vaccines against Plasmodium should include the CSP N-terminal region., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The circumsporozoite protein (CSP) of Plasmodium falciparum is a major surface protein, which forms a dense coat on the sporozoite's surface. Preclinical research on CSP and clinical evaluation of a CSP fragment-based RTS, S/AS01 vaccine have demonstrated a modest degree of protection against P. falciparum, mediated in part by humoral immunity and in part by cell-mediated immunity. Given the partial protective efficacy of the RTS, S/AS01 vaccine in a recent Phase 3 trial, further improvement of CSP-based vaccines is crucial. In this report, we describe the preclinical development of a full-length, recombinant CSP (rCSP)-based vaccine candidate against P. falciparum malaria suitable for current Good Manufacturing Practice (cGMP) production. Utilizing a novel high-throughput Pseudomonas fluorescens expression platform, we demonstrated greater efficacy of full-length rCSP as compared to N-terminally truncated versions, rapidly down-selected a promising lead vaccine candidate, and developed a high-yield purification process to express immunologically active, intact antigen for clinical trial material production. The rCSP, when formulated with various adjuvants, induced antigen-specific antibody responses as measured by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), as well as CD4+ T-cell responses as determined by ELISpot. The adjuvanted rCSP vaccine conferred protection in mice when challenged with transgenic P. berghei sporozoites containing the P. falciparum repeat region of CSP. Furthermore, heterologous prime/boost regimens with adjuvanted rCSP and an adenovirus type 35-vectored CSP (Ad35CS) showed modest improvements in eliciting CSP-specific T-cell responses and anti-malarial protection, depending on the order of vaccine delivery. Collectively, these data support the importance of further clinical development of adjuvanted rCSP, either as a stand-alone product or as one of the components in a heterologous prime/boost strategy, ultimately acting as an effective vaccine candidate for the mitigation of P. falciparum-induced malaria.