Francis O Eko
Morehouse School of Medicine, USA
Title: How a phage lysis protein transformed Vibrio cholerae into a vaccine delivery platform
Biography
Biography: Francis O Eko
Abstract
Statement of the Problem: Bacteriophage PhiX174 is an Escherichia coli-specific phage with a genome consisting of 11 genes. The phage encodes a single lysis gene E, the function of which is necessary and sufficient to induce lysis of E. coli. The resulting lysis protein E is a polypeptide of 91 amino acids and is devoid of any enzymatic activity. We previously showed that expression of the cloned lysis gene E causes lysis of Gram-negative bacteria. We have designed a versatile vaccine delivery platform based on the unique gene E-mediated lysis of Vibrio cholerae, which offers an exceptional opportunity to develop vaccines against different pathogens. Moreover, this platform is self-adjuvanting and capable of simultaneously delivering multiple vaccine antigens to the immune system. It also offers an attractive approach for developing combination vaccines, especially against diseases with epidemiological overlap. Here, we present data showing a utility of the VCG platform for induction of protective immunity even in the absence of external adjuvants.
Method: Groups of mice were Immunized Rectally (IR) or Intramuscularly (IM) with VCG expressing the Chlamydia trachomatis porin B and polymorphic membrane protein D proteins (rVCG-PmpD/PorB) or glycoprotein D from HSV-2 (rVCG-gD2) as antigen control. Vaccine efficacy was assessed by evaluating the intensity and duration of genital chlamydia shedding following intra vaginal challenge with live chlamydiae. Analysis of Variance (ANOVA) was used to compare differences between groups.
Findings: We demonstrated that both IM and IR immunization of mice with the rVCG vaccine elicited high levels of antigen-specific Th1 cell-mediated and humoral immune responses in mucosal and systemic tissues. Also, immunization reduced the length and intensity of genital chlamydial shedding following intra vaginal challenge with live chlamydiae, irrespective of route of vaccine administration.
Conclusion: These results highlight the potential of the VCG platform for eliciting immunity in the female genital tract via both mucosal and systemic delivery of antigens in the absence of external adjuvants.