142nd APHA Annual Meeting and Exposition

Home Events & Meetings Annual Meeting Schedule & Program

Online Program

Annual Meeting Recordings are now available for purchase

313658
Vectored antibody gene delivery protects mice against sporozoite challenge

142nd APHA Annual Meeting and Exposition (November 15 - November 19, 2014): http://www.apha.org/events-and-meetings/annual
Monday, November 17, 2014

Cailin Deal, PhD , Molecular Microbiology and Immunology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Alejandro Balazs, PhD , Ragon Institute of MGH, MIT & Harvard, Cambridge, MA
Diego Espinosa , Molecular Microbiology and Immunology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Fidel Zavala, MD , Molecular Microbiology and Immunology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
David Baltimore, PhD , Division of Biology, California Institute of Technology, Pasadena, CA
Gary Ketner, PhD , Molecular Microbiology and Immunology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Plasmodium sporozoites can be neutralized in vitro by monoclonal antibodies (MAb) against the circumsporozoite protein (CSP) and can block liver invasion in vivo by sporozoites of a transgenic rodent parasite that expresses P. falciparum CSP (Pb-Pf), preventing infection in mice.  Despite this, attempts at targeting CSP for a vaccine have fallen short of expectations, in part due to inability to induce durable high-titer antibodies.  A single un-neutralized sporozoite can initiate infection, necessitating sustained high-titer neutralizing antibodies for lasting protection.

Recently, David Baltimore’s laboratory developed an adeno-associated virus type 8 (AAV8) platform that efficiently delivers pre-formed MAb genes in vivo and directs sustained, high-level MAb production.  With the Baltimore lab, we have adopted that technology to express humanized MAbs against the central repeat region of the CSP protein of P. falciparum in mice.  Mice developed high titer human IgG antibodies as early as 1 week post transduction and levels have remained constant for more than 44 weeks at 200 to 1000 µg of IgG/ml.  70 percent of mice transduced with CSP MAb humanized 2A10 (h2A10), and challenged intravenously with 104 Pb-Pf sporozoites, reduced parasite liver burden to below the level of detection and 70 percent of h2A10-transduced mice were sterilely protected from a mosquito bite challenge.  Examination of antibody levels in individual mice revealed that all mice with human IgG concentrations above 1mg/mL were completely protected. This suggests that exceeding this antibody threshold results in consistent sterile protection and establishes that vectored MAb gene delivery has the potential to be an effective form of malaria control.  

Learning Areas:

Basic medical science applied in public health
Protection of the public in relation to communicable diseases including prevention or control
Public health biology

Learning Objectives:
Compare the advantages and disadvantages of traditional vaccination methods vs engineered immunity. Evaluate the use of vectored immunoprophylaxis as a means for malaria control. Discuss the potential utility of vectored immunoprophylaxis for other infectious diseases.

Keyword(s): Pathogens

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I have performed all of the data presented on the poster as this data was a portion of my thesis dissertation. My dissertation and scientific interests revolve around the use of viruses as vectors for vaccines and immunotherapeutics.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.

Back to: 3189.0: Delta Omega Poster Session I