vaccines-gynecologic-oncology-2018-posters

Page 90

Journal of Clinical Immunology and Allergy

ISSN: 2471-304X

E u r o p e a n C o n g r e s s o n

Vaccines & Vaccination

and Gynecologic Oncology

Vaccines & Vaccination and Gynecologic Oncology 2018

O c t o b e r 2 6 - 2 7 , 2 0 1 8

B u d a p e s t , H u n g a r y

truly effective HIV vaccinewill likely require rapid and robust elicitation of broadly neutralizing antibodies (bNAbs), but the pathways

to achieve this remain elusive. A critical roadblock has been the lack of practical animal models for reliably tracking development

of bNAb responses to HIV vaccination. This talk will overview the various humanized immunoglobulin mouse strains we and others

have collectively developed and/or are using for HIV vaccine research over the last decade, in order to highlight how they are helping

to rank candidate regions in the HIV-1 envelope (Env), for which it may be most feasible for vaccination to induce bnAbs against. First,

the pre- and post-immunization repertoires of various bNAb knock-in (KI) models we have engineered to produce unmutated precursor

B-cells of various prototype bNAbs will be presented, to illustrate how such models can be effective tools in pinpointing mechanisms

limiting bNAb development. Then, bNAb responses elicited in two of our recent knock-in models will be described, which are specifi-

cally directed to the V2 apex (a region in Env to which bNAb responses in infected donors arise more rapidly and frequently, and require

less somatic mutation to develop), to further support the notion that the V2 apex may be a relatively more tractable HIV vaccine target.

Our KI’s V2 apex-specific responses will also be presented to demonstrate how such models can serve as practical lead testing plat-

forms to iteratively down-select HIV immunogens or vaccine regimens re-designed to more selectively trigger bNAb responses and/or

overcome any remaining impediments to their induction.

Broadly neutralizing antibody knock-in models

as lead discovery platforms for identifying new

HIV vaccine approaches

Laurent K Verkoczy

Duke University, USA

Journal of Clinical Immunology and Allergy, Volume: 4

DOI: 10.21767/2471-304X-C2-006

Euro Vaccines 2018