First-in-Human PfSPZ-LARC2 Vaccination/CHMI

The primary objective of this study is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Powerful Sequencing Tool Helps Identify Infectious Diseases in Mali

NIAID Now |

Two scientists are shown at the University of Sciences, Techniques, and Technologies of Bamako, Mali, performing testing on plasma specimens from patients.

Malian scientists at the University of Sciences, Techniques, and Technologies of Bamako, Mali, perform VirCapSeq-VERT testing on plasma specimens from patients with unknown fevers. Shown are Dr. Fousseyni Kane (left) and Dr. Dramane Diallo (right).

Credit: Credit: Amadou Kone (CDC)

Powerful Sequencing Tool Helps Identify Infectious Diseases in Mali

An advanced diagnostic tool used in an observational clinical study in Bamako, Mali, helped identify infectious viruses in hospital patients that normally would have required many traditional tests. Scientists, led by the National Institute of Allergy and Infectious Diseases (NIAID), designed the study to help physicians identify the causes of unexplained fever in patients and to bring awareness to new technology in a resource-limited region.

Because malaria is the most common fever-causing illness in rural sub-Saharan Africa, most medical workers in the region presume patients with a fever have malaria. But recent NIAID work has identified dengue, Zika and chikungunya viruses – like malaria, all spread by mosquitos – in some Malian residents.

The observational study of 108 patients, published recently in The American Journal of Tropical Medicine and Hygiene, added the advanced diagnostic test, known as VirCapSeq-VERT, to traditional testing methods to identify cases of measles, SARS-CoV-2, HIV, and other viral diseases in patients. Surprisingly, more than 40% of patients were found to have more than one infection.

VirCapSeq-VERT is the virome capture-sequencing platform for vertebrate viruses, a powerful DNA sequencing technique capable of finding all viruses known to infect humans and animals in specimens, such as plasma. VirCapSeq-VERT uses special probes that capture all virus DNA and RNA in a specimen, even if the researcher does not know which specific virus to look for. Scientists then sequence the captured DNA and RNA to identify viruses present to solve the mystery of which viral infection(s) a patient has.

In the study, the researchers recommend that combining VirCapSeq-VERT with traditional diagnostic tests could greatly assist physicians “in settings with large disease burdens or high rates of coinfections and may lead to better outcomes for patients.”

Scientists from NIAID’s Division of Clinical Research collaborated on the project from July 2020 to October 2022 with colleagues from the University of Sciences, Techniques, and Technologies of Bamako, Mali, and Columbia University.

Reference: A Koné, et al. Adding Virome Capture Metagenomic Sequencing to Conventional Laboratory Testing Increases Unknown Fever Etiology Determination in Bamako, Mali. The American Journal of Tropical Medicine and Hygiene DOI: https://doi.org/10.4269/ajtmh.24-0449 (2024).

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Fabiano Oliveira, M.D., Ph.D.

Section or Unit Name
Vector Molecular Biology Section

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New Tool Identifies Aedes Mosquito Exposure in People

May 1, 2024

NIAID-developed test could be used to find hot spots for disease-spreading mosquitoes.

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Section/Unit: Location
Rockville, MD
This Researcher/Clinician’s Person Page
Fabiano Oliveira, M.D., Ph.D.
Parent Lab/Program
Laboratory of Malaria and Vector Research
Program Description

Our research focuses on the complex interactions between the human immune system and insect-derived molecules, and how these interactions can influence the outcomes of vector-borne diseases such as dengue, Zika, Chikungunya, and leishmaniasis. When an insect bites, it injects hundreds of arthropod molecules into the host's skin, alerting our immune system to these foreign agents. If the insect is infected with a pathogen, the microorganism is delivered along with these insect-derived molecules. Our immune response to these molecules over time can either help or hinder pathogen establishment, ultimately affecting the disease outcome.

Our work is conducted at two primary locations: the Laboratory of Malaria and Vector Research (LMVR) in Rockville, which is equipped with cutting-edge technologies, and the NIAID International Center of Excellence in Research (ICER) in Cambodia, where we conduct field observations and studies.

At LMVR-Rockville, we use advanced technologies and methodologies to explore the molecular and immunological mechanisms underlying the human response to arthropod bites and the pathogens they transmit. In Cambodia, at the NIAID ICER, we engage in extensive fieldwork to gather critical data and observations directly from affected populations. By integrating field data with laboratory findings, we aim to develop robust hypotheses that can lead to effective strategies for disease mitigation and control.

Our multidisciplinary approach allows us to bridge the gap between laboratory research and field applications. By understanding how the human immune system responds to arthropod molecules, we can identify potential targets for vaccines, therapeutics, and diagnostic tools. Additionally, our research contributes to the development of innovative vector control strategies that can reduce the incidence of these debilitating diseases.

Through collaboration with local communities, healthcare providers, and international partners, we strive to translate our scientific discoveries into practical solutions that can improve public health outcomes. Our ultimate goal is to reduce the burden of vector-borne diseases and enhance the quality of life for people living in endemic regions.

Our research aims to improve dengue prevention and treatment strategies for U.S. travelers, personnel in endemic areas, and regions with reported dengue cases, such as Hawaii, Florida, Texas, Puerto Rico, the U.S. Virgin Islands, and Guam. Enhanced predictive, management, diagnostic, and preventive measures for dengue outbreaks are particularly crucial for these at-risk regions. The development and use of prophylactic therapeutics targeting specific immune responses to mosquito bites could reduce the transmission of arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and West Nile viruses. Improved diagnostic capabilities for vector-borne diseases and emerging infections will lead to better patient outcomes. 

Clinical Studies
Selected Publications

Manning JE, Chea S, Parker DM, Bohl JA, Lay S, Mateja A, Man S, Nhek S, Ponce A, Sreng S, Kong D, Kimsan S, Meneses C, Fay MP, Suon S, Huy R, Lon C, Leang R, Oliveira F. Development of Inapparent Dengue Associated With Increased Antibody Levels to Aedes aegypti Salivary Proteins: A Longitudinal Dengue Cohort in Cambodia. J Infect Dis. 2022 Oct 17;226(8):1327-1337.

Guerrero D, Vo HTM, Lon C, Bohl JA, Nhik S, Chea S, Man S, Sreng S, Pacheco AR, Ly S, Sath R, Lay S, Missé D, Huy R, Leang R, Kry H, Valenzuela JG, Oliveira F, Cantaert T, Manning JE. Evaluation of cutaneous immune response in a controlled human in vivo model of mosquito bites. Nat Commun. 2022 Nov 17;13(1):7036.

Chea S, Willen L, Nhek S, Ly P, Tang K, Oristian J, Salas-Carrillo R, Ponce A, Leon PCV, Kong D, Ly S, Sath R, Lon C, Leang R, Huy R, Yek C, Valenzuela JG, Calvo E, Manning JE, Oliveira F. Antibodies to Aedes aegypti D7L salivary proteins as a new serological tool to estimate human exposure to Aedes mosquitoes. Front Immunol. 2024 May 1;15:1368066.

Guimaraes-Costa AB, Shannon JP, Waclawiak I, Oliveira J, Meneses C, de Castro W, Wen X, Brzostowski J, Serafim TD, Andersen JF, Hickman HD, Kamhawi S, Valenzuela JG, Oliveira F. A sand fly salivary protein acts as a neutrophil chemoattractant. Nat Commun. 2021 May 28;12(1):3213.

Oliveira F, Rowton E, Aslan H, Gomes R, Castrovinci PA, Alvarenga PH, Abdeladhim M, Teixeira C, Meneses C, Kleeman LT, Guimarães-Costa AB, Rowland TE, Gilmore D, Doumbia S, Reed SG, Lawyer PG, Andersen JF, Kamhawi S, Valenzuela JG. A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates. Sci Transl Med. 2015 Jun 3;7(290):290ra90.

Manning JE, Oliveira F, Coutinho-Abreu IV, Herbert S, Meneses C, Kamhawi S, Baus HA, Han A, Czajkowski L, Rosas LA, Cervantes-Medina A, Athota R, Reed S, Mateja A, Hunsberger S, James E, Pleguezuelos O, Stoloff G, Valenzuela JG, Memoli MJ. Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial. Lancet. 2020 Jun 27;395(10242):1998-2007.

Visit PubMed for a complete publication listing.

Additional Information

Articles

A tropical parasite, passed through the bite of a sand fly, is causing skin infections in the US

Major Areas of Research
  • Characterization of human immune response to ticks, mosquito, and sand fly saliva in the context of medically significant vector-borne diseases (Lyme disease, Powassan, dengue, malaria, and leishmaniasis)
  • Clinical and field epidemiology of the impact of mosquito saliva immunity on the outcome of dengue, Zika, and other diseases carried by mosquitos
  • Strategies to block vector-borne diseases by targeting the arthropod vector and interruption transmission to the human host

NIH Researchers Discover Novel Class of Anti-Malaria Antibodies

New antibodies that bind to a previously untargeted portion of the malaria parasite could lead to new monoclonal antibody treatments and vaccines for malaria.

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Global Research Led by UT Health San Antonio Uncovers Critical Weakness in Malaria Parasite

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Funded-research
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Link URL
https://news.uthscsa.edu/global-research-led-by-ut-health-san-antonio-uncovers-critical-weakness-in-malaria-parasite-2/
Research Institution
The University of Texas Health Science Center at San Antonio
Short Title
Global Research Led by UT Health San Antonio Uncovers Critical Weakness in Malaria Parasite
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Claudia Wair
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Jennifer Routh

First Vaccine Against Blood-Stage Malaria Is Well-Tolerated and Offers Effective Protection

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Funded-research
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Link URL
https://www.ox.ac.uk/news/2024-12-11-first-vaccine-against-blood-stage-malaria-well-tolerated-and-offers-effective
Research Institution
University of Oxford
Short Title
First Vaccine Against Blood-Stage Malaria Is Well-Tolerated and Offers Effective Protection
Content Coordinator
Claudia Wair
Content Manager
Jennifer Routh

New NOSI Prioritizes Malaria Vaccine and Monoclonal Antibody Discovery

Funding News Editions:
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Apply to NIAID’s Notice of Special Interest (NOSI): Accelerating Malaria Vaccine and Monoclonal Antibody Discovery if you can propose research that helps generate new malaria vaccine candidates or monoclonal antibody (mAb)-based interventions, especially for Plasmodium falciparum and P. vivax.

Recently, the World Health Organization (WHO) recommended two malaria vaccines, RTS/AS01E and R21/Matrix M, for broad introduction in African countries for children older than 5 months. To address future effective global malaria control and elimination, WHO issued revised Preferred Product Characteristics (PPC) calling for new strategic priorities for next generation malaria vaccines.  

Research Objectives and Scope 

Currently, due to significant scientific and technical challenges facing malaria research and development, there are very few preclinical and clinical candidates in the global development pipeline that possess promising features that meet the PPC-defined criteria. 

NIAID encourages applications focused on “combination” vaccine concepts to improve efficacy, targeting one or more parasite antigens of the different life cycle stages (i.e., pre-erythrocytic stage, blood, or sexual stage) of the parasites. 

Research Areas of Interest 

NIAID is most interested in the research topics listed below.

For vaccines: 

  • Identifying, characterizing, credentialing, or validating novel protective malaria antigens/peptides/epitopes.  
  • Molecular immunogen design and testing using cutting-edge innovations (e.g., artificial intelligence, machine learning, cryo-electron microscopy, structural immunobiology). 
  • Discovering new vaccine candidates based on novel technology platforms, adjuvants, or vaccination strategies. 
  • Constructing novel whole organism-based malaria vaccines or improvements to existing whole organism-based malaria vaccines. 
  • Discovering novel vaccine candidates or formulations that exhibit improved performance, manufacturability, or deliverability over existing vaccines. 
  • Discovering new vaccine candidates or improvement of existing vaccine candidates to have more favorable storage conditions, or administration and deployment features. 
  • Screening, testing, credentialing, or validating new vaccine candidates or formulations with novel assays or animal models. 

For mAbs or novel Ab-based interventions: 

  • Identifying and characterizing new functional mAbs, including broadly protective mAbs. 
  • Antibody engineering to improve functionality or stability, such as affinity/avidity, pharmacokinetic durability, or manufacturability. 
  • Developing novel platforms or strategies to express or deliver Abs or Ab-based products, including construction and testing of Ab-based concepts, such as viral-vectored, mRNA expressed, or bi- or multi-specific Ab constructs for improved product features to enhance prevention of malaria infection or transmission, or ameliorate malaria disease. 

Application and Submission Information 

This notice applies to application receipt dates on or after February 5, 2025, and subsequent receipt dates through November 16, 2027. 

Apply to this initiative through one of the following notices of funding opportunities (NOFOs) or any reissues of these NOFOs through the expiration date of this notice. 

Follow all instructions in the SF 424 (R&R) Application Guide and the NOFO you use to apply. You must include “NOT-AI-24-072” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF 424 R&R form.  

Inquiries  

Direct all inquiries to NIAID’s scientific/research contact, Dr. Annie Mo, at moa@niaid.nih.gov or 240-627-3320.

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