Lahari Das Poster 2024

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Dr Lahari Das

Albert Einstein College of Medicine, United States of America (USA)

A Novel Recombinant Herpes Simplex Virus -2 based Vaccine Against Tuberculosis


Poster Abstract

Tuberculosis (TB) remains an important health issue in developing and under-developed nations. The need of the hour is to develop a TB vaccine that protects better than the BCG and is able to elicit an effective and sustained immune response against Mtb. The role of antibodies in controlling Mtb infections is least explored. Many recent studies suggest that antibodies could play an important role in intracellular killing of Mtb. We propose that antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell killing (ADCK) can be important mechanisms that would help in controlling Mtb in the host.

A paradigm-shifting vaccine vector based on an attenuated herpes simplex type 2 (HSV-2) vector, ΔgD-2, was developed in our laboratory. We have demonstrated that immunization with ΔgD-2 not only induces HSV-specific FcƴRIV activating ADCC (IgG2c) antibodies that impart 100% protection against HSV-2 challenge, but it is also an efficient vaccine platform to deliver selected transgenes from other pathogens (E.g. Influenza). To overcome the limited capacity for transgene insertion into ΔgD-2 genome, we have engineered a second generation recombinant HSV-2 vector, Δg(GJDI)-2, by deleting the viral glycoproteins G, J, D, and I. Additionally, we have developed a unique recombination method for inserting transgenes into the Δg(GJDI)-2 viral genome based on the Bxb1 serine integrase system.

This allows high throughput cloning of multiple vaccine antigens using integrative plasmids that also encode for mammalian transmembrane domain and IgGκ leader sequence for surface localization of cloned antigen. We are expressing a number of TB antigens (PstS1, DnaK, Ag85B, GroEL, Cfp21, etc.) in Δg(GJDI)-2 vector and have found TB-specific antibody response in mice. These candidates are being evaluated for their ability to confer ADCC antibody-mediated protection against Mtb challenge. Thus, this recombinant HSV-2 virus expressing TB antigens would be the first effective antibody-based vaccine against TB.