FDA Postgraduate Research Opportunity in Live Attenuated Viral Vectors

A research opportunity is available in the Division of Viral Products (DVP), Office of Vaccines Research and Review (OVRR), at the Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA) in Silver Spring, Maryland.

The goal of this project is to enhance vaccine potency by expressing each desired vaccine antigen in a live viral vector. The vector is the rubella vaccine strain, which has demonstrated its safety and potency in millions of children each year. In this project, we will insert a foreign gene into the structural insertion site of the rubella virus genome. As a result, every time the rubella vector infects a cell it also expresses the new vaccine insert. This combines the safety and potency of the vector with the antigenicity of the vaccine insert.

For example, the insert can be SIV gag protein. Rubella can accommodate the entire SIV gag protein p27. This gene is stably expressed for more than 10 passages in cell culture. It is also expressed when the vector grows in vivo. This results in strong antibody titers and T cell immunity against SIV gag that are comparable to SIV infection. This may lead to immune protection against SIV infection.

Similarly, the insert can be the CSP protein of malaria. Antibodies specific for CSP can protect against malaria infection. One quarter of the world's population are at risk of malaria, and there is no vaccine. The rubella/CSP vectors are designed to establish sufficient immunity in young children to protect against severe malarial disease and reduce lethal disease in this age group. 

Recently, we found that certain host cell proteins can be expressed by rubella. If we make antibodies against certain cell proteins on the surface of lymphocytes, this may allow us to modulate the function of an entire cell subset. For example, antibodies to CD20, CD4, or CD8 could wipe out the effector functions of B cells, helper T cells, or cytolytic T cells. respectively if given separately. But, if given pairwise, they could modulate the function of all lymphocytes. We have successfully expressed CD20, and this may be a gateway vaccine for other subsets. The new vectors have expressed both type I and type II membrane proteins.

Under the guidance of a mentor, the participant will be involved in the following training activities:

Over the course of this opportunity, we are looking for growth in planning experiments and analyzing results. The selected participant will also participate in choosing new target antigens for greater vaccine potency.

This program, administered by ORAU through its contract with the U.S. Department of Energy to manage the Oak Ridge Institute for Science and Education, was established through an interagency agreement between DOE and FDA. The initial appointment is for one year, but may be renewed upon recommendation of FDA contingent on the availability of funds. The participant will receive a monthly stipend commensurate with educational level and experience. Proof of health insurance is required for participation in this program. The appointment is full-time at FDA in the Silver Spring, Maryland, area. Participants do not become employees of FDA, DOE or the program administrator, and there are no employment-related benefits.

The qualified candidate should have received a bachelor's degree in one of the relevant fields, or be currently pursuing the degree and will reach completion by the appointment start date. Degree must have been received within five years of the appointment start date.

If you have questions, send an email to ORISE.FDA.CBER@orau.org. Please include the reference code for this opportunity (FDA-CBER-2020-0043) in your email.