FDA Postdoctoral Research Opportunity in Live Attenuated Viral Vectors
*Applications will be reviewed on a rolling-basis.
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 a 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. During 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 expresses both its own proteins and 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. The result may be immune protection against SIV infection.
Similarly, the insert can be malaria CSP protein. 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 malarial infection and reduce lethal disease in this age group.
Recently, we have found that certain host cell proteins can be expressed by rubella. If we make antibodies against certain cell proteins on the surface of lymphocytes, we can knock out 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 if given separately. But, if given together, they could modulate the function of all lymphocytes. We have succeeded in expressing CD20, and this may be a gateway construct for the others. This includes both type I and type II membrane proteins.
Under the guidance of a mentor, the participant will be involved in the following training activities:
- Using creativity to identify good target antigens
- Vaccine design to incorporate known targets of protective antibodies into the vectors
- Perform studies in molecular virology to find out what is stably expressed in cell culture, what will grow in vivo, and which constructs will enhance the immune response when grown in vivo
CBER has animal facilities that provide unique access to macaques for immunization studies of vaccine structure and immune function.
Learning objectives for this project include: vaccine design, improving skills in molecular biology, analyzing vector growth and protein expression, and performing in vitro assays that predict immune function in vivo.
Over the course of this opportunity, we are looking for growth in planning experiments and analyzing results. This will include opportunities to solve problems in protein expression and stability. The selected participant will also participate in choosing new target antigens for greater vaccine potency.
Qualifications
The qualified candidate should have received a doctoral degree in one of the relevant fields. Degree must have been received within five years of the appointment start date.
Preferred skills:
- Ability to collaborate well in a group
- Ability to learn how to give and receive constructive criticism
- Training in molecular biology, virology and immunology
- Experience in vaccine design, protein expression, and in immunological assays to evaluate antiviral effects of antibodies and T cells
If you have questions, send an email to ORISE.FDA.CBER@orau.org. Please include the reference code for this opportunity (FDA-CBER-2020-0009) in your email.