Dataset Information

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

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.

SUBMITTER: Wang S

PROVIDER: S-EPMC5718816 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

Wang Shixia S Chou Te-Hui TH Hackett Anthony A Efros Veronica V Wang Yan Y Han Dong D Wallace Aaron A Chen Yuxin Y Hu Guangnan G Liu Shuying S Clapham Paul P Arthos James J Montefiori David D Lu Shan S

Human vaccines & immunotherapeutics 20170921 12

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 ...[more]

PMID: 28933684

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Project description:Infectious bronchitis virus (IBV) has been frequently reported in chickens worldwide, including in the Eastern Region of Saudi Arabia (ERS). Several IBV outbreaks were recently reported in chickens despite the massive use of various vaccines. Based on partial sequencing of the S1 gene, at least three genotypes were reported (CK/CH/LDL/97I, IS/720/99, and IS/Variant2/98) in the ERS with no available homologous vaccines. Herein, we tried to evaluate the protection provided by some selected commercial-available vaccines against these three genotypes. We divided the experimental chickens into eight groups. Representative isolates from these genotypes were inoculated into three groups of broiler chickens vaccinated with the H-120 vaccine at the age of 1 day and boosted with the 4/91 vaccine at the age of 14 days (challenged groups). One group of chickens had received the same protocol of IBV vaccines but was kept without infection to serve as a vaccine control group. The three isolates were inoculated into three other similar but unvaccinated groups of broiler chickens (infected groups). Group eight chickens were neither vaccinated nor infected and used as a negative control group. Evaluation of the protection induced by the tested vaccination schedule was assessed by several criteria, including the ability to reduce the severe clinical signs caused by IBV infection, changes in the body temperature of various groups of chickens, the reduction in the magnitude of IBV-induced lesions, and the reduction in the viral loads in tracheas of a different group of chicken. Monitoring the immune status of chickens was also recorded based on the hemagglutination inhibition antibodies in sera of various groups of chickens. Our results show clinical and tracheal protection against IBV/IS/Variant2/98-like and IBV/IS/720/99-like strains. Moderate protection was observed in the IBV/CK/CH/LDL/97I-like pressure. The kidneys of the challenged groups of chickens showed minimal or no gross lesions compared with the infected groups, even in those chickens challenged with the IBV/CK/CH/LDL/97I-like strain. In conclusion, this is the first study to perform the protectotyping of some IBV strains from Saudi Arabia. It demonstrated the proficiency of the investigated vaccination schedule in control of infection of broiler chickens with IBV/IS/Variant2/98 and IBV/IS/720/99 strains. It is highly recommended to introduce the homologous IBV/CK/CH/LDL/97I-based vaccine to the vaccination protocols of chickens in the ERS to match the circulating strains and ensure better protection.

Dataset Information

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

Publications

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

Similar Datasets

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