Human vaccines & immunotherapeutics
-
Hum Vaccin Immunother · Jan 2014
Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes fatal acute lung infections in critically ill individuals. Its pathogenesis is associated with bacterial virulence conferred by the type III secretion system (TTSS), through which P. aeruginosa causes necrosis of the lung epithelium and disseminates into the circulation, resulting in bacteremia, sepsis, and mortality. TTSS allows P. aeruginosa to directly translocate cytotoxins into eukaryotic cells, inducing cell death. ⋯ Both the rabbit polyclonal anti-PcrV antibody and the murine monoclonal anti-PcrV antibody, mAb166, inhibit TTS toxin translocation. mAb166 IgG was cloned, and a molecular engineered humanized anti-PcrV IgG antigen-binding fragment, KB001, was developed for clinical use. KB001 is currently undergoing Phase-II clinical trials for ventilator-associated pneumonia in France and chronic pneumonia in cystic fibrosis in USA. In these studies, KB001 has demonstrated its safety, a favorable pharmacokinetic profile, and promising potential as a nonantibiotic strategy to reduce airway inflammation and damage in P. aeruginosa pneumonia.
-
Hum Vaccin Immunother · Jan 2014
Burden of vaccine-preventable disease in adult Medicaid and commercially insured populations: analysis of claims-based databases, 2006–2010.
Vaccination rates among United States (US) adults are suboptimal, resulting in morbidity, mortality, and financial burden attributable to potentially vaccine-preventable diseases (VPDs). Unadjusted annual incidence proportions of VPDs were estimated for Medicaid and commercially insured adults aged 19-64 years using 2006-2010 claims, along with age/gender-adjusted incidence proportions for 2010. ⋯ Age/gender-adjusted incidence proportions (per 100 000) in 2010 among Medicaid vs commercially insured adults for meningococcal disease were 26.2 (95% CI 22.9-29.8) vs 2.0 (1.9-2.2) (P < 0.001); hepatitis B 88.9 (82.6-95.6) vs 17.5 (17.0-17.9) (P < 0.001); pneumococcal disease 98.2 (91.7-105.1) vs 21.1 (20.7-21.6) (P < 0.001); hepatitis A 19.8 (16.9-23.1) vs 4.5 (4.3-4.7) (P < 0.001); mumps 2.1 (1.3-3.3) vs 1.4 (1.3-1.6) (P = 0.14); measles 0.3 (0.1-1.0) vs 0.3 (0.2-0.3) (P = 0.38); herpes zoster (60- to 64-year-olds only) 459 (408-515) vs 473 (466-481) (P = 0.35); varicella (19- to 39-year-olds only) 6.5 (4.8-8.5) vs 8.0 (7.5-8.5) (P = 0.12); influenza 586 (573-598) vs 633 (631-636) (P < 0.001); and pertussis 1.8 (1.1-2.8) vs 3.2 (3.0-3.4) (P < 0.001). Research is needed to fully understand the causes of the disparity of the coded incidence of some VPDs in adult Medicaid population than commercially insured adults in the US.
-
The pneumococcus is a remarkably adaptable pathogen whose disease manifestations range from mucosal surface infections such as acute otitis media and pneumonia to invasive infections such as sepsis and meningitis. Currently approved vaccines target the polysaccharide capsule, of which there are over 90 distinct serotypes, leading to rapid serotype replacement in vaccinated populations. ⋯ An area attracting considerable attention is the potential application of live attenuated vaccines to confer serotype-independent protection against mucosal and systemic infection. On the basis of recent work to understand the mucosal and systemic responses to nasal administration of pneumococci and to develop novel attenuation strategies, the prospect of a practical and protective live vaccine remains promising.
-
Hum Vaccin Immunother · Jan 2014
Potential impact of vaccination against Neisseria meningitidis on Neisseria gonorrhoeae in the United States: results from a decision-analysis model.
Components in 4CMenB vaccine against Neisseria meningitidis serogroup B have shown to potentially cross-react with Neisseria gonorrhoeae. We modeled the theoretical impact of a US 4CMenB vaccination program on gonorrhea outcomes. A decision-analysis model was populated using published healthcare utilization and cost data. ⋯ At a cost of $75,000 per QALY gained, and incremental to the vaccine's effect on meningococcal disease, a price of $26.10 (95% CrI, $9.10-$57.20) per dose, incremental to the price of the meningococcal vaccine, would be justified from the societal perspective. At this price, the net cost per infection averted would be $1,677 (95% CrI, $404-$2,564). Even if the cross-immunity of 4CMenB vaccine and gonorrhea is only 20%, the reduction in gonorrhea infections and associated costs would be substantial.
-
Hum Vaccin Immunother · Jan 2014
Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.
Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. ⋯ We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.