Research Focus

Our Interests

A major focus in Andrabi laboratory is to utilize in vitro directed evolution platform combined with structure-guided design approaches to develop vaccine immunogens against complex pathogens such as HIV, Influenza virus, Arenaviruses and Coronaviruses. The other major area of research in the laboratory is to understand the immunological basis of B cell affinity maturation pathways to complex antigen surfaces, both in vaccination and in infection and to utilize this information for designing more effective vaccines. The overall goal is to design vaccine immunogens and immunization strategies that can induce protective broadly neutralizing antibody responses against complex pathogens through vaccination in humans.

 

Vaccine design strategy showing germline targeting, B-cell immunofocusing, antibody maturation, and iterative vaccine development and testing.

The figure summarizes the Andrabi Laboratory's research approach for developing vaccines against complex pathogens such as HIV, influenza viruses, arenaviruses, and coronaviruses.The upper section, labeled "Approach," depicts a staged process for inducing broadly neutralizing antibody (bnAb) responses. Germline-targeting immunogens and nanoparticle-based immunogens are used to activate rare bnAb precursor B cells. Subsequent immunofocusing immunogens concentrate immune responses on desired antibody targets. Additional immunogen refinement, labeled "Polishing," employs diverse native HIV envelope trimer immunogens to further mature and broaden antibody responses.A funnel-shaped diagram illustrates the progression from a diverse population of precursor B cells to a smaller population of highly specific B cells. Alongside the funnel, a vertical arrow indicates increasing germline activation, expansion of epitope-specific B cells, and antibody maturation and breadth. A panel labeled "Specificities" shows selection for B cells recognizing a target epitope of interest while reducing responses to other epitopes.The lower section, labeled "Major Research Areas," presents an iterative vaccine design cycle consisting of three interconnected research activities:

  1. Vaccine engineering by directed evolution, where immunogens undergo mutation, screening, selection, and testing.
  2. Animal model evaluation, using multiple animal systems and transgenic models to assess vaccine candidates.
  3. Analysis of immune responses, including laboratory and computational methods used to characterize antibodies and immune cell responses.

Arrows connect these activities in a continuous cycle labeled "Iterative vaccine design," illustrating how experimental results inform the design of improved vaccine immunogens.

Immune Design Principles:

  1. Rational vaccine engineering to target rare bnAb B cell precursors: (Germline-Targeting: affinity/avidity ⇡⇡⇡)
  2. BnAb site grafting on scaffolds or nanoparticles: (Scaffolding or Multivalent Display)
  3. mmunofocus bnAb B cell responses and reduce immunodominance: (Immunofocusing)
  4. Designs that mimic native-like spike protein configurations: (Native Spike Mimics)

 

Diagram showing a stepwise HIV vaccine strategy that activates rare bnAb precursor B cells, focuses immune responses, and promotes antibody maturation.

This diagram illustrates a stepwise strategy for eliciting broadly neutralizing antibodies (bnAbs) against HIV.

  1. Germline-targeting immunogen and nanoparticle presentation are used to activate rare precursor B cells capable of developing into bnAb-producing cells. This stage is labeled "Rare bnAb B cell activation."

  2. Activated B cells are exposed to an immunofocusing immunogen, which directs immune responses toward a specific viral epitope of interest while reducing responses to competing, non-protective targets. This stage is labeled "B cell Immunofocusing."

  3. Additional vaccine boosts using a diverse cocktail of native HIV envelope (Env) trimers further stimulate and refine antibody responses. A stage called "Polishing" represents repeated optimization of antibody recognition through exposure to diverse antigen variants.

  4. The central funnel illustrates selection and maturation of precursor B cells over time. A diverse population of B cells at the top is progressively narrowed through successive immunizations, enriching B cells that recognize the desired epitope.

  5. A gradient arrow on the right shows progression from germline (GL) activation, through expansion of epitope-specific B cells, to maturation and broadening of antibody responses.

  6. The specificity panel indicates that, during maturation, immune responses become increasingly focused on the epitope of interest, while responses to other epitopes are reduced.