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Exploration of a Sequential Gp140-Gp145 Immunization Regimen with Heterologous Envs to Induce a Protective Cross-Reactive HIV Neutralizing Antibody Response In Non-human Primates
- Source :
- Virologica Sinica
- Publication Year :
- 2021
- Publisher :
- Springer Singapore, 2021.
-
Abstract
- Raising a heterologous tier 2 neutralizing antibody (nAb) response remains a daunting task for HIV vaccine development. In this study, we explored the utility of diverse HIV-1 envelope (Env) immunogens in a sequential immunization scheme as a solution to this task. This exploration stemmed from the rationale that gp145, a membrane-bound truncation form of HIV Env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode. We first showed that gp140 DNA prime-gp145 Tiantan vaccinia (TV) boost likely represents a general format for inducing potent nAb response in mice. However, when examined in rhesus macaque, this modality showed little effectiveness. To improve the efficacy, we extended the original modality by adding a strong protein boost, namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle (NP), which was generated by a newly developed click approach. The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule. Importantly, the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge. Collectively, our studies highlighted that diversification of Env immunogens, in both types and formulations, under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development. Electronic supplementary material The online version of this article (10.1007/s12250-021-00361-3) contains supplementary material, which is available to authorized users.
- Subjects :
- Immunology
Heterologous
Viremia
HIV Infections
Biology
HIV Antibodies
Sequential immunization
chemistry.chemical_compound
Mice
Nanoparticle
Virology
medicine
Animals
HIV vaccine
Neutralizing antibody
Broadly neutralizing antibodies (bnAbs)
Human immunodeficiency virus type 1 (HIV-1)
AIDS Vaccines
env Gene Products, Human Immunodeficiency Virus
biology.organism_classification
medicine.disease
Antibodies, Neutralizing
Macaca mulatta
Regimen
Rhesus macaque
chemistry
Immunization
biology.protein
HIV-1
Molecular Medicine
Native-like Env trimers
Vaccinia
Vaccine
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 1995820X and 16740769
- Database :
- OpenAIRE
- Journal :
- Virologica Sinica
- Accession number :
- edsair.doi.dedup.....716cbdf0ceafca23ba99430c5faa13b7