p.2
Mechanisms of bnAbs in HIV-1
What are some specific sites that bnAbs target?
V3 Glycan, V1V2 Glycan, CD4bs, Interface, Fusion peptide, MPER.
p.13
Dengue Virus and Immune Response
How is the Dengue virus primarily transmitted?
Through mosquito-borne virus infection.
p.10
Therapeutic Applications of bnAbs
What does the prefix in therapeutic antibody nomenclature signify?
The prefix often indicates the species from which the antibody is derived.
p.7
Challenges in bnAb Induction
What is a major roadblock for the evolution of broadly neutralizing antibodies (bnAbs)?
The reasons for their limited elicitation in individuals are not fully understood.
p.3
Broadly Neutralizing Antibodies (bnAbs)
What are broadly neutralizing antibodies (bnAbs)?
Potent antibodies that protect against HIV-1.
p.5
HIV-1 Envelope Variability
What are gp41 stumps and gp120 shedding?
Features of HIV-1 Env that complicate immune recognition.
p.3
Broadly Neutralizing Antibodies (bnAbs)
What range of HIV-1 subtypes are bnAbs active against?
A wide range of HIV-1 subtypes.
p.7
Vaccine Development for bnAbs
What factors can potentially be engaged to develop bnAb vaccines?
Host factors, immune environment, and viral/antigen factors.
p.1
Mechanisms of bnAbs in HIV-1
How do bnAbs perform in studies?
They protect in vitro and in animal studies in vivo.
p.12
Broadly Neutralizing Antibodies (bnAbs
What are broadly neutralizing antibodies (bnAbs)?
Antibodies that can neutralize a wide range of viral strains.
p.12
Broadly Neutralizing Antibodies (bnAbs
In which viral diseases have bnAbs been discovered?
HIV, Influenza, Norovirus, Hepatitis C Virus, CMV, Ebola, Adenovirus.
p.12
Vaccine Development for bnAbs
What is the focus of current efforts regarding bnAbs?
To develop bnAb-based vaccines for various infections.
p.1
Broadly Neutralizing Antibodies (bnAbs)
What are broadly neutralizing antibodies (bnAbs)?
Potent antibodies that protect against HIV-1 in vitro and in vivo.
p.3
Mechanisms of bnAbs in HIV-1
What do bnAbs target on the HIV-1 virus?
The intact, closed trimer via multiple sites.
p.2
Factors Influencing bnAb Elicitation
Do bnAbs develop in all patients?
No, they only develop in some patients.
p.10
Therapeutic Applications of bnAbs
What does the nomenclature of therapeutic antibodies typically include?
It includes prefixes, infixes, and suffixes that indicate the source, type, and target of the antibody.
p.4
Challenges in bnAb Induction
What is the current focus of the field regarding bnAb induction?
To define immunogens that elicit bnAbs and identify roadblocks to bnAb induction.
p.4
Challenges in bnAb Induction
What has been the success of bnAb induction by vaccination so far?
There has been no success in inducing bnAbs by vaccination thus far.
p.8
Somatic Mutations in bnAbs
What is biochemical characterization in the context of bnAbs?
Biochemical characterization involves analyzing the properties and interactions of bnAbs at a molecular level.
p.7
Mechanisms of bnAbs in HIV-1
Are only distinct Env proteins capable of inducing bnAb activity?
It is unclear if only distinct Env proteins can induce bnAb activity.
p.10
Therapeutic Applications of bnAbs
What is the primary focus of the document regarding therapeutic antibodies?
Nomenclature of therapeutic antibodies.
p.1
Broadly Neutralizing Antibodies (bnAbs)
Against how many HIV-1 subtypes are bnAbs active?
A wide range of HIV-1 subtypes.
p.1
Mechanisms of bnAbs in HIV-1
What do bnAbs target on the HIV-1 virus?
The intact, closed trimer via multiple sites.
p.8
Therapeutic Applications of bnAbs
What does bnAb cloning involve?
bnAb cloning involves isolating and characterizing antibodies that can neutralize a wide range of viral strains.
p.11
Therapeutic Applications of bnAbs
Why is epitope accessibility important for antiviral antibodies?
It affects neutralization and effector functions.
p.11
Therapeutic Applications of bnAbs
What does epitope density refer to in the context of antiviral antibodies?
The concentration of epitopes available for antibody binding.
p.5
HIV-1 Envelope Variability
Why is HIV-1 Env a difficult target for antibodies?
Due to low density Env expression and high antigenic variability.
p.7
Challenges in bnAb Induction
Why are potent bnAbs only elicited in a small fraction of individuals?
The specific reasons are unclear and may involve various factors.
p.7
Factors Influencing bnAb Elicitation
What factors may influence the elicitation of bnAbs?
Host, viral, or disease factors could be decisive.
p.2
Mechanisms of bnAbs in HIV-1
What do bnAbs target on the HIV-1 virus?
The intact, closed trimer via multiple sites.
p.5
HIV-1 Envelope Variability
Why is the neutralization relevant closed trimer of HIV-1 Env not stable?
Due to its structural characteristics and variability.
p.10
Therapeutic Applications of bnAbs
Why is nomenclature important in the context of therapeutic antibodies?
It helps in standardizing the naming conventions for better communication and understanding in the field.
p.4
Therapeutic Applications of bnAbs
What have animal studies shown regarding bnAbs?
They have been successful in demonstrating the potential of bnAbs as therapeutics.
p.1
Factors Influencing bnAb Elicitation
Do bnAbs develop in all patients?
No, they only develop in some patients.
p.8
Broadly Neutralizing Antibodies (bnAbs)
How can novel antibodies and immunogens be defined?
Novel antibodies and immunogens can be defined through their unique structures and functions that elicit specific immune responses.
p.4
Mechanisms of bnAbs in HIV-1
What do bnAbs target on the HIV-1 virus?
Multiple epitopes on the HIV-1 envelope trimer.
p.11
Therapeutic Applications of bnAbs
What are the desired features of antiviral antibodies?
Long half-life, low immunogenicity, and no off-target effects.
p.2
Broadly Neutralizing Antibodies (bnAbs
What are broadly neutralizing antibodies (bnAbs)?
Potent antibodies that protect against HIV-1 in vitro and in vivo.
p.5
HIV-1 Envelope Variability
What contributes to the structural challenges of HIV-1 Env?
Structural flexibility and conformational shielding.
p.3
Mechanisms of bnAbs in HIV-1
How do bnAbs perform in studies?
They protect in vitro and in animal studies in vivo.
p.5
HIV-1 Envelope Variability
How does the immune system perceive HIV-1 Env?
It sees a range of Env products, including alternate closed and minimally opened conformations.
p.6
Somatic Mutations in bnAbs
What is a characteristic feature of broadly neutralizing antibodies (bNAbs)?
They frequently have long CDRH3 regions.
p.12
Vaccine Development for bnAbs
Which infections have the most advanced bnAb-based vaccine efforts?
Influenza, HIV, and Norovirus.
p.4
Broadly Neutralizing Antibodies (bnAbs)
What are bnAbs?
Broadly neutralizing antibodies that target multiple epitopes on the HIV-1 envelope trimer.
p.3
Factors Influencing bnAb Elicitation
Do bnAbs develop in all patients?
No, they only develop in some patients.
p.6
Somatic Mutations in bnAbs
How do somatic mutations in bNAbs compare to non-HIV IgG?
Non-HIV IgG carry 15 – 20 VH-gene somatic mutations, while potent bNAbs carry 40 – 100 VH-gene mutations.
p.6
Factors Influencing bnAb Elicitation
What questions arise regarding the high mutation rate in bNAbs?
What triggers this? Is the high mutation rate needed for function? How can this be triggered by vaccination?
p.10
Therapeutic Applications of bnAbs
What is a common suffix used in the nomenclature of therapeutic antibodies?
The suffix '-mab' indicates that the molecule is a monoclonal antibody.
p.6
Somatic Mutations in bnAbs
What unusual features do broadly neutralizing HIV-1 antibodies have?
They have an unusually high degree of somatic mutations in both CDR and FWR regions.
p.4
Therapeutic Applications of bnAbs
What is a promising finding related to bnAb treatment?
It can delay or reduce virus replication.
p.8
Mechanisms of bnAbs in HIV-1
What is the significance of tracing the viral antigen that triggered bnAb?
Tracing the viral antigen helps in understanding the immune response and the development of broadly neutralizing antibodies.
p.13
Dengue Virus and Immune Response
Does infection with one serotype of Dengue provide protection against others?
No, it does not provide protection.
p.4
Therapeutic Applications of bnAbs
What have small-scale human studies shown about bnAbs?
They have shown promising findings.
p.11
Therapeutic Applications of bnAbs
How does differential glycosylation affect antiviral antibodies?
It influences Fc epitope accessibility and antibody function.
p.8
Therapeutic Applications of bnAbs
What is the goal of creating therapeutic bnAbs?
The goal is to develop antibodies that can effectively neutralize a wide range of viral infections for therapeutic use.
p.4
Broadly Neutralizing Antibodies (bnAbs)
What type of antibodies have been discovered in the context of bnAbs?
Highly potent and broad antibodies.
p.13
Dengue Virus and Immune Response
What serious complications are associated with secondary Dengue infections?
Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS).
p.8
Mechanisms of bnAbs in HIV-1
What is functional characterization of bnAbs?
Functional characterization assesses the ability of bnAbs to neutralize viruses and their mechanisms of action.
p.8
Factors Influencing bnAb Elicitation
What is a germline ancestor in the context of bnAbs?
A germline ancestor refers to the original antibody structure from which a broadly neutralizing antibody evolves.
p.8
Vaccine Development for bnAbs
Why is it important to design immunogens that bind to the germline ancestor?
Designing immunogens that bind to the germline ancestor can enhance the elicitation of bnAbs during vaccination.
p.11
Therapeutic Applications of bnAbs
What is the significance of epitope accessibility during viral entry?
It is crucial for effective neutralization by antibodies.