# Presentation: 064966

## SECTION OF RETROVIRAL PATHOGENESIS
Hana Golding, Ph.D. (PI, Lab Chief)
Keith Peden, Ph.D. (PI)
Marina Zaitseva, Ph.D. (Senior Staff Fellow) 

SECTION OF RETROVIRAL IMMUNOLOGY
	Dennis Klinman, MD, Ph.D. (PI)

SECTION OF MOLECULAR RETROVIROLOGY
	Arifa Khan, Ph.D. (PI)

**Hana Golding, Ph.D. (PI, Lab Chief)**
**Keith Peden, Ph.D. (PI)**
**Marina Zaitseva, Ph.D. (Senior Staff Fellow)**
**SECTION OF RETROVIRAL IMMUNOLOGY**
- 	**Dennis Klinman, MD, Ph.D. (PI)**
**SECTION OF MOLECULAR RETROVIROLOGY**
- 	**Arifa Khan, Ph.D**. **(PI)**

_**LABORATORY OF RETROVIRUS RESEARCH:**__**LAB STRUCTURE**_

## Review of HIV vaccines (pre-IND, original IND submissions, IND amendments, pre-BLA, BLA)
Provide expert opinions to other CBER Laboratories and Divisions on:
Novel Cell Substrates
Adventitious agents detection
Retrovirus contamination
Lentivirus vectors
Plasmid DNA vaccines
CpG oligonucleotides and other adjuvants

**Provide expert opinions to other CBER Laboratories and Divisions on:**
**Novel Cell Substrates**
**Adventitious agents detection**
**Retrovirus contamination**
**Lentivirus vectors**
**Plasmid DNA vaccines**
**CpG oligonucleotides and other adjuvants**

_**LABORATORY OF RETROVIRUS RESEARCH:**__**REGULATORY MISSION (I) **_

## 
Presentations to CBER Advisory Committees
Presentations to the World Health Organization and to other international regulatory authorities
Participation in Interagency Working Groups 
Organization and/or participation in special workshops on HIV vaccines, plasmid DNA vaccines, and novel cell substrates

**Presentations to CBER Advisory Committees**
**Presentations to the World Health Organization and to other international regulatory authorities**
**Participation in Interagency Working Groups **
**Organization and/or participation in special workshops on HIV vaccines, plasmid DNA vaccines, and novel cell substrates**

_**LABORATORY OF RETROVIRUS RESEARCH:**__**REGULATORY MISSION (II) **_

## 	Preparation of  Guidance Documents for sponsors of new vaccines: 
Considerations for plasmid DNA vaccines for infectious disease indications (Klinman)
Characterization  and qualification of cell substrates and other biological starting  materials for the production of viral vaccines (Peden, Khan)
Preclinical toxicity assessments of preventive vaccines to support phase 1 clinical trials (Golding)

***Considerations for plasmid DNA vaccines for infectious disease indications ******(Klinman)***
***Characterization  and qualification of cell substrates and other biological starting  materials for the production of viral vaccines ******(Peden, Khan)***
***Preclinical toxicity assessments of preventive vaccines to support phase 1 clinical trials ******(Golding)***

_**LABORATORY OF RETROVIRUS RESEARCH:**__**REGULATORY MISSION (III) **_

## SECTION OF RETROVIRAL IMMUNOLOGY Dennis Klinman (PI)

**Monitor the  Safety and Immunomodulatory Activity of **
**DNA-based Products ****	**
**DNA-based products regulated by the FDA:**
**DNA vaccines**
**Synthetic oligodeoxynucleotides (ODN) for therapy, immune modulation, adjuvants**
**Regulated products in which DNA exists as a “contaminant”:**
**Proteins produced in bacteria containing bacterial DNA.**
**Vaccines produced in mammalian cell lines containing mammalian DNA****.**

## Dennis Klinman : Accomplishments

**Discovered and patented a new class of **_**stimulatory**_** CpG ODN.**
**vaccine adjuvants**
**immunoprotective agents**
**anti-allergens.**
**Discovered and patented a new class of **_**suppressive**_** ODN.**
**for prevention or treatment of autoimmune and inflammatory diseases.**
**mechanism of action of these ODN.**

## SECTION OF RETROVIRAL PATHOGENESIS Hana Golding (PI)

**STUDIES ON HIV CELL ENTRY**
**HIV coreceptor expression and function in primary human cells **
**new entry inhibitors targeting the HIV coreceptor CCR5**
**HIV VACCINE TRIALS **
**new HIV EIA for differential diagnosis of HIV infections in the presence of vaccine-generated antibodies **
**COUNTER TERRORISM PREPAREDNESS**** **
**new *****in vitro***** assays and animal models for evaluation of smallpox vaccines potency and safety.**

## Hana Golding: Accomplishments

**Uninfected vaccine trial participants score negative, while all HIV infections are diagnosed early**
**Simple and economical test. Can be implemented in sites of future HIV vaccine trials and in blood collection centers around the globe. **
**SMALLPOX VACCINE EVALUATION**
**Reporter-gene based vaccinia neutralization assay (high throughput)**
**Collaborative work on monkeypox primate challenge for “2-animal rule”**
**Mouse models for tracking vaccinia dissemination: vaccine safety and post-exposure prophylaxis**
*** ***

**Hana Golding: Accomplishments**

## SECTION OF RETROVIRAL PATHOGENESISMarina Zaitseva (Senior Staff Fellow): Accomplishments

**	****CELLULAR GENES INVOLVED IN THYMIC RECONSTITUTION AND IMMUNE MODULATION**
**Murine models of transient thymic atrophy: **
**	****low-dose irradiation; dexamethasone; estrogen.  **
**Use models to  identify salvage mechanisms important for thymic regeneration.**
**	**

## Marina Zaitseva (Senior Satff  Fellow) 

**	****CELLULAR GENES INVOLVED IN  IMMUNE RECONSTITUTION**
**ongoing experiments in irradiated mice: reconstitution of T cells in the Gut-associated lymphoid tissues**

## SECTION OF RETROVIRAL PATHOGENESIS Keith Peden (PI)

- •	Safety of tumorigenic cell substrates for vaccine manufacture
- • 	SV40 contamination in human vaccines
- • 	HIV coreceptor evolution and pathogenesis
**	****	**

## Keith Peden: Accomplishments 

**	****	****Animal models to assess the ****	****	****	****oncogenic activity of cellular DNA**
**	****	**- combination of oncogene-expressing  plasmids induced 	  tumors in newborn mice.
- ready to test DNA from new cell-substrate
**	****Quantitative assays to measure infectivity of integrated retroviral DNA**
- 	-	 estimates for safe levels of residual cell-substrate DNA in 	 viral vaccines
-    -  tools to evaluate removal of cellular DNA

## Keith Peden: Accomplishments (2)

- •	**quantitative assays to detect the presence of primate polyomavirus DNA in biological specimens**** **
**single-cycle, reporter-gene based neutralization assays for BKV, JCV, and SV40**

## 
Simian Foamy Virus Transmission Studies
- 	assess  risk of human infection by SFV-infected blood donors. 
Studies of Simian Foamy Virus Replication
- 	potential risk of SFV propagation in simian and human cells used for vaccine manufacturing. 	

**Simian Foamy Virus Transmission Studies**
- - 	**assess  risk of human infection by SFV-infected blood donors. **
**Studies of Simian Foamy Virus Replication**
**- ****	****potential risk of SFV propagation in simian and human cells used for vaccine manufacturing. ****	**

**MOLECULAR RETROVIROLOGY SECTION  **
**	****Arifa Khan (PI): Accomplishments**

##  	Strategies for Detection of Infectious Agents in Vaccine Cell Substrates

quantitative assays for detection of  retroviruses 
induction of endogenous retroviruses in cells from different animal species
induction of HHV-8 as a model of latent DNA virus  

**quantitative assays for detection of  retroviruses **
**induction of endogenous retroviruses in cells from different animal species**
**induction of HHV-8 as a model of latent DNA virus **** **

**	****Arifa Khan: Accomplishments**** **