Marina Ulanova MD, PhD

NOSM University
955 Oliver Road
Thunder Bay ON  P7B 5E1  Canada
Phone: 807-766-7340
Fax: 807-766-7362
Email: marina.ulanova@nosm.ca
Dr. Ulanova’s Website

2000-2005

1995-2000

1994

1992

1988-1992

1980-1982

1978-1980

1972-1978

1. The role of NOD-like receptors and inflammasome activation in innate immunity to pathogenic bacteria

Intracellular NOD-like receptors (NLR) sense pathogen-associated molecular patterns and “danger signals” and consequently mediate host response leading to pathogen elimination. Activation of NLRs results in the assembly of inflammasomes required for the activation of caspase-1 followed by IL-1beta precursor processing into the biologically active IL-1beta.

Haemophilus influenzae is an important Gram-negative pathogen able to cause severe invasive infections, such as sepsis and meningitis. The most virulent strains express a polysaccharide capsule that protects the bacteria against immune defenses. The capsules of various strains differ in chemical structure; six serotypes (a-f) are distinguished based on the antigenic properties of capsular polysaccharides. The most virulent is serotype b (Hib) followed by serotype a (Hia). Certain H. influenzae strains do not have a capsule and are less virulent than the encapsulated ones.

Although the role of adaptive immunity in host defense against encapsulated H. influenzae is well established, the role of innate immunity is poorly understood. My group investigates molecular mechanisms of interactions of the polysaccharide capsule with innate immune cells using an in vitro model of infection of human monocytes by various H. influenzae strains including wild-type encapsulated bacteria of different serotypes, mutant strains that lost the capsule expression, as well as naturally occurring non-encapsulated bacteria (NTHi).  We also study molecular mechanisms of interactions between the Gram-negative opportunistic pathogen Pseudomonasaeruginosa and human cells, with specific focus on the role of NLRs in inflammatory responses induced by these bacteria.

2. Immunoepidemiology of infections caused by encapsulated bacteria in Northern Ontario

Modern vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have dramatically reduced the incidence of invasive diseases caused by these pathogens. However, during the last decade, an alarming trend towards an increased prevalence of infections caused by non-vaccine serotypes of H. influenzaeand S. pneumoniae have been noticed in many countries of the world. Moreover, the effectiveness of the vaccination significantly varies across different populations.

There are data on increased incidence rates of invasive infections caused by H. influenzae and S. pneumoniaein Aboriginal communities in Canada. We have recently found a high incidence of invasive H. influenzae type a (Hia) disease in Northwestern Ontario; clinical and demographic analyses have indicated that First Nations children aged <5 years and adults with predisposing medical conditions are most affected by invasive H. influenzae disease. It is important to understand what specific genetic, epigenetic, and/or environmental factors are responsible for an increased susceptibility of First Nations to severe infections caused by Hia. Such studies will be critical for prevention of invasive bacterial disease in this population. Our current research focuses on immunological mechanisms of defense against Hia in individuals of different age, ethnicity, and presenting with various medical conditions that can compromise the immune system. In collaboration with the National Microbiology Laboratory, National Research Council of Canada, and the Arctic Investigation Program of the US Centers of Disease Control and Prevention, we work towards the development of a new vaccine to prevent Hia disease in North American Aboriginal people.

3. Immune response of patients with severe chronic kidney disease to 13-valent pneumococcal conjugate vaccine (PCV13)

Patients with severe chronic kidney disease (CKD) are immunocompromised and known to have an increased risk of pneumococcal infection, i.e. invasive pneumococcal disease and pneumonia. The effect of currently used 23-valent pneumococcal polysaccharide vaccine (PPV23) in these patients is suboptimal because of their immune dysfunction. The second generation pneumococcal vaccines (polysaccharide-protein conjugate) have superior immunogenicity and show protective effect in some immunocompromised adult individuals.

We conduct Clinical Trial (registration number NCT02370069) to test whether previous immunization with PPV23 affects the immune response of CKD patients to PCV13. We immunize two groups of adult severe CKD patients undergoing haemodialysis in Thunder Bay Regional Health Sciences Centre with one dose of PCV13 and assess their immunological response, vaccine safety, and longevity of protection. The first group consists of patients without history of pneumococcal vaccination and the second group includes patients who had previously been immunized with PPV23. Immune response to immunization is assessed via the following analyses: 1) the levels of serum anti-capsular polysaccharide IgG and IgM against 13 individual serotypes included into PCV13 by ELISA; 2) in vitro functional antibody activity against 13 individual serotypes by a standardized multiplexed opsonophagocytic killing assay (OPA); 3) the numbers of total IgG and antigen-specific B-memory cells using ELISPOT.  The anticipated results will provide rationale for the optimal immunization strategy to prevent pneumococcal infection in a high risk population, i.e. in patients with severe CKD.

Complete publication list

Choi J, Nix EB, Gaultier GN, Cox AD, McCready W, Ulanova M. Naturally occurring bactericidal antibodies specific for Haemophilus influenzae lipooligosaccharide are present in healthy adult individuals. Vaccine 2015 Mar 1. pii: S0264-410X(15)00249-2. doi: 10.1016/j.vaccine.2015.02.060. [Epub ahead of print]

Nix EB, Williams K, Cox AD, St Michael F, Romero-Steiner S, Schmidt DS, McCready WG, Ulanova M. Naturally acquired antibodies against Haemophilus influenzae type a in Aboriginal adults, Canada. Emerg Infect Dis 2015; 21(2): 273-279

Poling J, Kelly L, Chan C, Fisman D, Ulanova M. Hospital admission for community acquired pneumonia in a First Nations population. Can J Rural Med 2014; 19 (4): 135-41

Cerqueira AM, Tsang RSW, Jamieson FB, Ulanova M. A case of acute epiglottitis caused by Haemophilus influenzae type a in an adult. JMM Case Reports 2014 DOI 10.1099/jmmcr.0.001552. Published online: 12 September 2014

Tsang RSW, Bruce MG, Lem M, Barreto L, Ulanova M. A review of invasive Haemophilus influenzae disease in the Indigenous populations of North America. Epidemiol Infect 2014; 142(7):1344-54

Choi J, Cox AD, Li J, McCready W, Ulanova M. Activation of Innate Immune Responses by Haemophilus influenzae Lipooligosaccharide. Clin Vaccine Immunol 2014; 21 (5): 769-76

Ulanova M, Tsang RSW.  Haemophilus influenzae serotype a as a cause of serious invasive infections. Lancet Inf Dis 2014; 14(1):70-82

Sadeghi-Aval PS, Werner J, Cerqueira A, Balfour-Boehm J, Ulanova M. Piceatannol modulates lung epithelial cellular responses to Pseudomonas aeruginosa. Inflamm Allergy Drug Targets 2013; 12 (5): 297-307

Ulanova M. Global Epidemiology of Invasive Haemophilus influenzae Type a Disease: Do We Need a New Vaccine? Journal of Vaccines 2013; Article ID 941461. View

Sadeghi-Aval P, Tsang RSW, Jamieson FB, Ulanova M. Emergence of non-type b encapsulated Haemophilus influenzae as a cause of pediatric meningitis in Northwestern Ontario. Can J Infect Dis Med Microbiol 2013; 24 (1): 13-16

Cerqueira A, Khaper N, Lees SJ, Ulanova M. The antioxidant resveratrol down-regulates inflammation in an in vitro model of Pseudomonas aeruginosa infection of lung epithelial cells. Can J Physiol Pharmacol 2013; 91(3): 248-55

Nix EB, Hawdon N, Gravelle S, Biman B, Brigden M, Malik S, McCready WG, Ferroni G, Ulanova M. Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era. Clin Vaccine Immunol 2012; 19: 766-9

Hawdon N, Nix EB, Tsang RS, Ferroni G, McCready WG, Ulanova M. Immune response to Haemophilusinfluenzae type b vaccination in patients with chronic renal failure. Clin Vaccine Immunol 2012; 19: 967-9

Hawdon N, Biman B, McCready WG, Brigden M, Malik S, Vergidis D, Kisselgoff O, Ulanova M. Antibody against Haemophilus influenzae protein D in patients with chronic conditions causing secondary immunodeficiency. Vaccine 2012; 30: 1235-8.

Ulanova M, Tsang R, Altman E.  Neglected infectious disease in Aboriginal communities: Haemophilus influenzae serotype a and Helicobacter pylori. Vaccine 2012; 30: 6960-6

Kelly L, Tsang R, Morgan A, Jamieson F, Ulanova M. Invasive disease caused by Haemophilus influenzae type a in Northern Ontario First Nations communities. J Med Microbiol 2011; 60: 384-390

Werner J, DeCarlo C, Escott N, Zehbe I, Ulanova M. Expression of integrins and Toll-like receptors in cervical cancer: effect of infectious agents. Innate Immun 2011; 18: 55-69

Hawdon N, Sadeghi Aval P, Barnes R, Gravelle S, Rosengren J, Khan S, Ciofu O, Johansen H, Høiby N, Ulanova M. Cellular responses of A549 alveolar epithelial cells to serially collected Pseudomonas aeruginosa from cystic fibrosis patients at different stages of pulmonary infection. FEMS Immunol Med Microbiol 2010; 59: 207-20

Gravelle S, Barnes R, Hawdon N, Shewchuk L, Eibl J, Lam JS, Ulanova M.  Up-regulation of integrin expression in lung adenocarcinoma cells caused by bacterial infection: in vitro study. Innate Immun 2010; 16: 14-26

Brown VM, Madden S, Kelly L, Jamieson FB, Tsang RS, Ulanova M. Invasive Haemophilus influenzae disease caused by non-type b strains in Northwestern Ontario, Canada, 2002-2008. Clin Infect Dis 2009; 49:1240-3

Ulanova M and Tsang R. Invasive Haemophilus influenzae disease: changing epidemiology and host-parasite interactions in the 21st century. Infect Genet Evol 2009; 9: 594-605

Ulanova M, Gravelle S, Barnes R. The role of epithelial integrin receptors in recognition of pulmonary pathogens. J Innate Immun 2009; 1: 1-14