Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.
Hum Vaccin Immunother
; 13(12): 2996-3009, 2017 12 02.
Article
in En
| MEDLINE
| ID: mdl-28933684
ABSTRACT
Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater than 50% of the viruses included in a high throughput PhenoSense neutralization assay when these immuongens were tested as a DNA prime followed by a fixed 5-valent gp120 protein vaccine boost. The new polyvalent formulation, using five gp120 immunogens selected from this subgroup, elicited improved quality of antibody responses in rabbits than the previous DP6-001 formulation. More significantly, this new polyvalent formulation elicited higher antibody responses against a panel of gp70V1/V2 antigens expressing V1/V2 sequences from diverse subtypes. Bioinformatics analysis supports the design of a 4-valent or 5-valent formulation using gp120 immunogens from this screening study to achieve a broad coverage against 16 HIV-1 subtypes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Antibodies
/
HIV Envelope Protein gp120
/
AIDS Vaccines
/
Vaccines, DNA
/
Antibodies, Neutralizing
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Animals
Language:
En
Journal:
Hum Vaccin Immunother
Year:
2017
Type:
Article
Affiliation country:
United States