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Parallel induction of CH505 B cell ontogeny-guided neutralizing antibodies and tHIVconsvX conserved mosaic-specific T cells against HIV-1
- Source :
- Molecular Therapy-Methods & Clinical Development, Molecular Therapy. Methods & Clinical Development
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation of broadly neutralizing antibody lineages and conserved-mosaic tHIVconsvX immunogens aiming to induce effective cross-clade T cell responses, were combined to assess vaccine interactions. These immunogens were delivered in heterologous vector/modality regimens consisting of non-replicating simian (chimpanzee) adenovirus ChAdOx1 (C), non-replicating poxvirus MVA (M), and adjuvanted protein (P). Outbred CD1-SWISS mice were vaccinated intramuscularly using either parallel CM8M (tHIVconsvX)/CPPP (CH505) or sequential CM16M (tHIVconsvX)/CPPP (CH505) protocols, the latter of which delivered T cell CM prior to the CH505 Env. CM8M (tHIVconsvX) and CPPP or CMMP (CH505) vaccinations alone were included as comparators. The vaccine-elicited HIV-1-specific trimer-binding and neutralizing Abs and CD8+/CD4+ T cell responses induced by the combined and comparator regimens were not statistically separable among regimens. The Ab-lineage immunogen strategy was particularly suited for combined regimens for its likely less potent induction of Env-specific T cell responses relative to homologous epitope-based vaccine strategies. These results inform design of the first rationally combined Ab and T cell vaccine regimens in human volunteers.
- Subjects :
- 0301 basic medicine
HIV vaccine
Immunogen
simian adenovirus
Heterologous
Biology
EnvSeq1
Article
Epitope
Virus
03 medical and health sciences
tHIVconsvX
0302 clinical medicine
Genetics
Conserved mosaic
Molecular Biology
T cell vaccine
broadly neutralizing antibodies
MVA
Virology
3. Good health
Vaccination
030104 developmental biology
CH505
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
conserved regions
Antibody
T-cell vaccine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy-Methods & Clinical Development, Molecular Therapy. Methods & Clinical Development
- Accession number :
- edsair.doi.dedup.....6de892e56c771293f6b87727ccfffe3f