Lisa Morici
Associate Professor
Biography
Research Interests
The emergence of multidrug resistant organisms represents the single greatest threat to our ability to successfully combat infectious diseases. In addition, the potential for deliberate misuse of biological organisms that are highly virulent or drug resistant has ushered the need for novel medical countermeasures against these “select agents”. To address these public health burdens, the lab of Dr. Lisa Morici focuses on three main areas of research:
- Novel vaccine platforms against intracellular bacteria
- Naturally-derived antimicrobials to treat multidrug resistant organisms
- In vitro and in vivo models of infection
Articles
Immunological considerations in the development of Pseudomonas aeruginosa vaccines
2019
Pseudomonas aeruginosa is an opportunistic human pathogen capable of causing a wide range of potentially life-threatening infections. With multidrug-resistant P. aeruginosa infections on the rise, the need for a rationally-designed vaccine against this pathogen is critical. A number of vaccine platforms have shown promising results in pre-clinical studies, but no vaccine has successfully advanced to licensure. Growing evidence suggests that an effective P. aeruginosa vaccine may require Th17-type CD4+ T cells to prevent infection. In this review, we summarize recent pre-clinical studies of P. aeruginosa vaccines, specifically focusing on those that induce Th17-type cellular immunity. We also highlight the importance of adjuvant selection and immunization route in vaccine design in order to target vaccine-induced immunity to infected tissues. Advances in cellular immunology and adjuvant biology may ultimately influence better P. aeruginosa vaccine platforms that can protect targeted human populations.
Intradermal vaccination with a Pseudomonas aeruginosa vaccine adjuvanted with a mutant bacterial ADP-ribosylating enterotoxin protects against acute pneumonia
2019
Respiratory infections are a leading cause of morbidity and mortality globally. This is partially due to a lack of effective vaccines and a clear understanding of how vaccination route and formulation influence protective immunity in mucosal tissues such as the lung. Pseudomonas aeruginosa is an opportunistic pathogen capable of causing acute pulmonary infections and is a leading cause of hospital-acquired and ventilator-associated pneumonia. With multidrug-resistant P. aeruginosa infections on the rise, the need for a vaccine against this pathogen is critical. Growing evidence suggests that a successful P. aeruginosa vaccine may require mucosal antibody and Th1- and Th17-type CD4+ T cells to prevent pulmonary infection. Intradermal immunization with adjuvants, such as the bacterial ADP-Ribosylating Enterotoxin Adjuvant (BARE) double mutant of E. coli heat-labile toxin (dmLT), can direct protective immune responses to mucosal tissues, including the lungs. We reasoned that intradermal immunization with P. aeruginosa outer membrane proteins (OMPs) adjuvanted with dmLT could drive neutralizing antibodies and migration of CD4+ T cells to the lungs and protect against P. aeruginosa pneumonia in a murine model. Here we show that mice immunized with OMPs and dmLT had significantly more antigen-specific IgG and Th1- and Th17-type CD4+ memory T cells in the pulmonary environment compared to control groups of mice. Furthermore, OMPs and dmLT immunized mice were significantly protected against an otherwise lethal lung infection. Protection was associated with early IFN-γ and IL-17 production in the lungs of immunized mice. These results indicate that intradermal immunization with dmLT can drive protective immunity to the lung mucosa and may be a viable vaccination strategy for a multitude of respiratory pathogens.
Novel multi‐component vaccine approaches for Burkholderia pseudomallei
2019
Burkholderia pseudomallei is the causative agent of melioidosis. Historically believed to be a relatively rare human disease in tropical countries, a recent study estimated that, worldwide, there are approximately 165 000 human melioidosis cases per year, more than half of whom die. The bacterium is inherently resistant to many antibiotics and treatment of the disease is often protracted and ineffective. There is no licensed vaccine against melioidosis, but a vaccine is predicted to be of value if used in high‐risk populations. There has been progress over the last decade in the pursuit of an effective vaccine against melioidosis. Animal models of disease including mouse and non‐human primates have been developed, and these models show that antibody responses play a key role in protection against melioidosis. Surprisingly, although B. pseudomallei is an intracellular pathogen there is limited evidence that CD8+ T cells play a role in protection. It is evident that a multi‐component vaccine, incorporating one or more protective antigens, will probably be essential for protection because of the pathogen's sophisticated virulence mechanisms as well as strain heterogeneity. Multi‐component vaccines in development include glycoconjugates, multivalent subunit preparations, outer membrane vesicles and other nano/microparticle platforms and live‐attenuated or inactivated bacteria. A consistent finding with vaccine candidates tested in mice is the ability to induce sterilizing immunity at low challenge doses and extended time to death at higher challenge doses. Further research to identify ways of eliciting more potent immune responses might provide a path for licensing an effective vaccine.
A Burkholderia pseudomallei Outer Membrane Vesicle Vaccine Provides Cross Protection against Inhalational Glanders in Mice and Non-Human Primates
2017
Burkholderia mallei is a Gram-negative, non-motile, facultative intracellular bacillus and the causative agent of glanders, a highly contagious zoonotic disease. B. mallei is naturally resistant to multiple antibiotics and there is concern for its potential use as a bioweapon, making the development of a vaccine against B. mallei of critical importance. We have previously demonstrated that immunization with multivalent outer membrane vesicles (OMV) derived from B. pseudomallei provide significant protection against pneumonic melioidosis. Given that many virulence determinants are highly conserved between the two species, we sought to determine if the B. pseudomallei OMV vaccine could cross-protect against B. mallei. We immunized C57Bl/6 mice and rhesus macaques with B. pseudomallei OMVs and subsequently challenged animals with aerosolized B. mallei. Immunization with B. pseudomallei OMVs significantly protected mice against B. mallei and the protection observed was comparable to that achieved with a live attenuated vaccine. OMV immunization induced the production of B.mallei-specific serum IgG and a mixed Th1/Th17 CD4 and CD8 T cell response in mice. Additionally, immunization of rhesus macaques with B. pseudomallei OMVs provided protection against glanders and induced B.mallei-specific serum IgG in non-human primates. These results demonstrate the ability of the multivalent OMV vaccine platform to elicit cross-protection against closely-related intracellular pathogens and to induce robust humoral and cellular immune responses against shared protective antigens.
Immunomodulatory effects of tick saliva on dermal cells exposed to Borrelia burgdorferi, the agent of Lyme disease
2016
The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin.
Media Appearances
Stopping whooping cough in its tracks
Another pertussis vaccine is being developed at Tulane University in New Orleans, Louisiana. “Our approach is not necessarily to replace the acellular pertussis vaccine, but to improve it by adding what is known as an adjuvant,” explains Lisa Morici, microbiologist and associate professor at Tulane University. An adjuvant is an additional substance delivered with a vaccine that enhances the long-term immune response. “What we need is to restore the T-cell, and in particular the TH17 cell, response that the whole-cell vaccine was able to enlist. We think we can do that by adding an adjuvant,” says Morici.
