Early mortality and recurrent hospitalizations due to invasive pneumococcal disease (Streptococcus pneumoniae infection) are common for people with Sickle Cell Disease (SCD). Frequent pneumococcal vaccinations are administered to SCD patients in the US, reducing infections and increasing patient life expectancy. Unfortunately, recent research indicates that the currently licensed pneumococcal vaccines are not as effective in patients with SCD, which is associated with low antibody titers after vaccination. Our group has shown that mice with SCD are not protected from infection after pneumococcal vaccination. Much like in SCD patients, we correlated this lack of protection with short-lived pneumococcal antibody titers after vaccination. An important finding from this work is that antibody titers do not recover after booster shots are given to SCD mice, indicating that there is a deficiency in the generation of both B-cell memory and long-lived plasma cells (which produce antibodies). Further compounding this problem, it has been shown that protective pneumococcal vaccine responses require specialized B-cells in the spleen and peritoneal cavity called B-1 B-cells, and we have previously shown that SCD mice have dramatically reduced numbers of B-1 cells in their spleens. We also observed reduced percentages of these cells in the blood of SCD patients when compared to healthy control subjects. Hence, we have found cellular and functional correlates in the SCD mouse model that may explain the reduced effectiveness of pneumococcal vaccines and increased susceptibility to infection in people with SCD. We are currently working on understanding the basic mechanism of impaired pneumococcal immunity in SCD mice, with the aim of developing new vaccines and therapeutics to overcome this problem.
Mycoplasma pneumoniae is a human respiratory pathogen and the etiological agent of many cases of bronchitis and community-acquired pneumonia. Infection with this bacterium can also cause and/or exacerbate other diseases, including asthma. Diagnosis is difficult as most medical laboratories do not screen for this pathogen, given that quick and inexpensive tests are not readily available. Common first-line β-lactam antibiotics are ineffective at treatmenting M. pneumoniae infection as this bacterium lacks a cell wall. Consequently, this pathogen is often overlooked during diagnosis of affected individuals, and common treatments do not target the source of the disease. This results in considerable economic and societal hardships due to lost and ineffective work/school time, making this pathogen a burden to public health. Unfortunately, several vaccine trials conducted in military personnel during the 1960s using inactivated bacteria resulted in minimal efficacy, and in some instances vaccination appeared to exacerbate disease upon subsequent challenge with virulent M. pneumoniae. We are working with the Geary lab in Pathobiology to overcome this problem and rationally design a new M. pneumoniae vaccine that lacks the safety issues that have plagued the field for decades.