Multivalent Vaccination Strategies With Novel HIV-1 Trimeric Envelope Proteins Elicit Improved Neutralizing Antibody Responses Compared to Monovalent Vaccination Regimens

DSpace/Manakin Repository

Multivalent Vaccination Strategies With Novel HIV-1 Trimeric Envelope Proteins Elicit Improved Neutralizing Antibody Responses Compared to Monovalent Vaccination Regimens

Citable link to this page

 

 
Title: Multivalent Vaccination Strategies With Novel HIV-1 Trimeric Envelope Proteins Elicit Improved Neutralizing Antibody Responses Compared to Monovalent Vaccination Regimens
Author: Bricault, Christine Ann ORCID  0000-0002-4741-605X
Citation: Bricault, Christine Ann. 2016. Multivalent Vaccination Strategies With Novel HIV-1 Trimeric Envelope Proteins Elicit Improved Neutralizing Antibody Responses Compared to Monovalent Vaccination Regimens. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
Access Status: This work is under embargo until 2019-05-01
Full Text & Related Files:
Abstract: Elicitation of neutralizing antibodies (NAbs) remains a major goal in the generation of a successful vaccine against human immunodeficiency virus type 1 (HIV-1). One of the major obstacles in generating such NAbs is the vast sequence diversity of their target, the HIV-1 envelope (Env) protein. This dissertation will describe multiple vaccination strategies utilizing a soluble form of Env (gp140) to address the sequence diversity of HIV-1 Env and to improve the NAb responses elicited through vaccination in the guinea pig model. A bioinformatically optimized mosaic gp140, designed as a single sequence to cover global HIV-1 sequence diversity, was utilized in combination with a clade C gp140, resulting in a complementary repertoire of NAbs when compared to vaccination with each single protein. Additionally, a quadrivalent mixture of four novel clade C gp140s with distinct antigenic properties was found to elicit a greater magnitude of NAbs when compared to any single protein in the mixture. Furthermore, longitudinal, heterologous prime/boost vaccination regimens resulted in binding antibodies to a greater number of distinct sequences within a single epitope of variable loop 2, and NAb of a greater magnitude, than a homologous prime/boost regimen. Finally, a panel of rationally designed variable loop 2 and 3 sequence modified trimers was designed. When utilized in a mixture, the variable loop 2 modified trimers elicited a greater magnitude and breadth of NAbs than the single, unmodified wild type protein alone. These data show that multivalent vaccination strategies with HIV-1 Env trimers result in improved NAb responses compared to single Env protein vaccinations and may help to guide the development of future vaccination regimens.
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493411
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters