Broadly Neutralizing Antibody-Guided Carbohydrate-Based HIV Vaccine Design: Challenges and Opportunities

ChemMedChem ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 357-362 ◽  
Author(s):  
Chang-Cheng Liu ◽  
Xiu-Jing Zheng ◽  
Xin-Shan Ye
Keyword(s):  
Vaccine Design ◽  
Neutralizing Antibody ◽  
Hiv Vaccine ◽  
Challenges And Opportunities ◽  
Broadly Neutralizing Antibody ◽  
Design Challenges

scholarly journals Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design

2012 ◽  
Vol 86 (8) ◽  
pp. 4688-4692 ◽  
Author(s):  
Mattia Bonsignori ◽  
David C. Montefiori ◽  
Xueling Wu ◽  
Xi Chen ◽  
Kwan-Ki Hwang ◽  
...  
Keyword(s):  
Vaccine Design ◽  
Neutralizing Antibody ◽  
Infected Donor ◽  
Broadly Neutralizing Antibody ◽  
Antibody Specificities ◽  
Hiv 1

HIV vaccine design and the neutralizing antibody problem

2004 ◽  
Vol 5 (3) ◽  
pp. 233-236 ◽  
Author(s):  
Dennis R Burton ◽  
Ronald C Desrosiers ◽  
Robert W Doms ◽  
Wayne C Koff ◽  
Peter D Kwong ◽  
...  
Keyword(s):  
Vaccine Design ◽  
Neutralizing Antibody ◽  
Hiv Vaccine

scholarly journals Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template

2018 ◽  
Author(s):  
Raiees Andrabi ◽  
Jesper Pallesen ◽  
Joel Allen ◽  
Ge Song ◽  
Jinsong Zhang ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Attractive Potential ◽  
Induced Responses ◽  
Potential Component ◽  
Broadly Neutralizing Antibody ◽  
Cross Neutralization

SummaryEpitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. Chimpanzee SIV Envelope (Env) shares a single bnAb site, the V2-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Accordingly, we generated a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determined the structure of the MT145K trimer by cryo-EM and showed its architecture was remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knock-in mouse with chimpanzee MT145K trimer induced HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induced responses exhibiting some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.

scholarly journals Distinct Immunoglobulin Fc Glycosylation Patterns Are Associated with Disease Nonprogression and Broadly Neutralizing Antibody Responses in Children with HIV Infection

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e00880-20
Author(s):  
M. Muenchhoff ◽  
A. W. Chung ◽  
J. Roider ◽  
Anne-Sophie Dugast ◽  
Simone Richardson ◽  
...  
Keyword(s):  
Potential Role ◽  
Sexual Debut ◽  
Neutralizing Antibody ◽  
Affinity Maturation ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Effector Functions ◽  
Systems Immunology ◽  
Broadly Neutralizing Antibody

ABSTRACTA prophylactic HIV vaccine would ideally induce protective immunity prior to sexual debut. Children develop broadly neutralizing antibody (bnAb) responses faster and at higher frequencies than adults, but little is known about the underlying mechanisms or the potential role of Fc-mediated effector functions in disease progression. We therefore performed systems immunology, with immunoglobulin profiling, on HIV-infected children with progressive and nonprogressive disease. Pediatric nonprogressors (PNPs) showed distinct immunoglobulin profiles with an increased ability to elicit potent Fc-mediated natural killer (NK)-cell effector functions. In contrast to previous reports in adults, both groups of children showed high levels of gp120-specific IgG Fc glycan sialylation compared to bulk IgG. Importantly, higher levels of Fc glycan sialylation were associated with increased bnAb breadth, providing the first evidence that Fc sialylation may drive affinity maturation of HIV-specific antibodies in children, a mechanism that could be exploited for vaccination strategies.IMPORTANCE To protect future generations against HIV, a vaccine will need to induce immunity by the time of sexual debut and hence requires immunization during childhood. Current strategies for a prophylactic HIV vaccine include the induction of a broadly neutralizing antibody response and the recruitment of potent effector functions of immune cells via the constant antibody Fc region. In this study, we show that nonprogressing HIV-infected children mounted antibody responses against HIV that were able to mediate potent Fc effector functions, which may contribute to the control of HIV replication. Children who had specific glycan structures on the Fc portion of antibodies against HIV were able to neutralize a broader range of HIV variants, providing evidence of a potential role of Fc glycovariation in the development of bnAbs against HIV. These findings complement our knowledge of the distinct immune landscape in early life that could be exploited in the development of vaccine strategies.

Sign in / Sign up

Export Citation Format

Share Document