Vaccines and vaccine immunology
Vaccines are one of the main pillars sustaining public health. Anti-viral vaccines in particular have been extremely successful in providing protection against potentially deadly viral infections such as polio, chickenpox, rubella and measles. However, conventional vaccine strategies are inadequate for developing protective vaccines against many other pathogenic viruses, such as human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV), or for developing a more broadly protective vaccine against influenza. Indeed, it has become increasingly clear that new strategies are needed to develop vaccines that can cope with the diversity and variability exhibited by HIV and HCV or the sudden introduction of a potentially pandemic flu virus.
Research in the Pantophlet Lab is focused on probing novel immunogen design strategies and immunization modalities to elicit antibodies with capacity to protect against HIV-1 and offer better protection against flu. Such antibodies, generally termed broadly neutralizing antibodies (bnAbs), target epitopes that are largely invariable among otherwise diverse strains.
The overall objective of our activities is thus to contribute to the development of an effective HIV vaccine and better flu vaccines. To this end, studies on the ontogeny of bnAb responses and molecular details of bnAb:epitope interactions are used to illuminate strategies in the Pantophlet Lab pertaining to the molecular and chemical engineering of immunogens for evoking bnAb responses. The iterative design of immunogens is informed by characterizing (neutralizing) antibody responses to select immunogens in novel animal models.
Our research objectives are driven by five complementary aims:
- To interrogate naïve B cell receptor interactions with designer immunogens in vitro
- To probe immunogen design concepts in human antibody transgenic animal models
- To explore application of novel adjuvants and immunomodulatory platforms in vivo
- To investigate the relevance of T follicular helper cell and T memory cell responses in vivo
- To dissect B cell responses in-depth at the serological, cellular and monoclonal level
We apply several techniques and methodologies in the lab that are rooted in immunochemistry, biochemistry, microbiology, molecular biology, immunology, and virology. The main lab includes a thermocycler, warm incubators and shakers, temperature-controlled table-top centrifuges and microcentrifuges, several heat blocks, a +4°C lab fridge, -20°C freezers, a -80°C freezer, protein and nucleic acid gel-electrophoresis apparatuses, a Nanovue, an ELISA plate reader and plate washer, a high-performance microplate luminometer, an ÄKTA FPLC with MALS and RI detectors and an Octet RED96e biolayer interferometer. Multiple desktop PCs are available for data analyses and other research-related work.
Directly connected to the main lab are a dedicated tissue culture room, a chemicals room and and a large shared walk-in cold room. The tissue culture room includes BSCs, a temperature-controlled table-top centrifuge, a large-capacity CO2 incubator, two non-CO2 incubators, an additional thermocycler, an inverted microscope and a -20°C freezer. The chemicals room is used for buffer and reagent preparation and chemicals storage and the cold room for storage of items by lab members and for conducting overnight experiments that require refrigeration.
Lab members also have nearby access to shared equipment, including a GelDoc system, a state-of-the art qPCR instrument, a 10X Chromium Controller, and a Flow Cytometry Laboratory with instruments for cell analyses and sorting. Autoclaves and a dishwashing system are also available nearby for cleaning and sterilizing labware and for disposal of biohazardous waste. Animal work is supported by Animal Care Services and contract research organizations.
Research in the Pantophlet Lab is supported by operating grants from the Canadian Institutes of Health Research (CIHR) and the National Institute of Allergy and Infectious Diseases (NIAID) of the United States. Dr. Pantophlet is supported by a Career Scholar award from the Michael Smith Foundation for Health Research (MSFHR) in British Columbia. Funding for the development of lab infrastructure has been secured from the Canada Foundation for Innovation (CFI) and the British Columbia Knowledge Development Fund (BCKDF) of the B.C. Ministry of Jobs, Trade and Technology.