One of the major obstacles to developing a HIV vaccine is defining adjuvants and immunogens that induce persistent HIV antigen specific systemic and mucosal humoral responses of high magnitude. Our recent studies evaluating a novel TLR7/8 ligand (3M052) from 3M Pharmaceuticals formulated in biodegradable synthetic polymer nanoparticles in RMs has for the first time yielded HIV Env specific long-lived plasma cells (LLPCs) in the macaque bone marrow for close to one year post final vaccination. The presence of LLPCs correlated significantly with binding, neutralizing and ADCC activity bearing antibody responses that also persisted at high magnitude for a year. Robust and persistent germinal center, follicular t helper cells and lymph node resident plasma cells were also observed in draining lymph nodes in these macaques. Finally, the persistent response was observed to be dependent on the presence of the novel 3M052 adjuvant alone and combining with a TLR4 agonist did not further enhance immune responses in contrast to our observations in mice. However, we have faced considerable challenges in translating our in house developed polymer particle formulations in industrial scale up for human use. Therefore, building on our proof of concept studies, the goal of the current proposal is to: a) systematically evaluate a clinical formulation (cGMP scalable oil emulsion based nanoparticle) developed in partnership with 3M pharmaceuticals and the Infectious Disease Research Institute (IDRI) in its ability to induce these potent Env specific LLPCs in macaques for expedited translation for use in humans and b) carefully dissect the innate and B cell based molecular mechanisms by which the 3M052 adjuvant is capable of promoting Env specific LLPCs and long lived antibody responses.

Public Health Relevance

HIV-1 mediated AIDS is one among many infectious diseases that is not preventable by a vaccine. Our project is aiming at validating and studying immune responses to a very promising HIV vaccine approach and candidate in non-human primates (Rhesus monkeys) to expedite translation of this vaccine for use in humans.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01OD023039-03
Application #
9536173
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hild, Sheri Ann
Project Start
2016-08-08
Project End
2019-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322