Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.

BACKGROUND: Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. METHODS: Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 µg) on days 0, 14, and 28. Another group (N=8) received the 240 µg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined. RESULTS: There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 µg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery. CONCLUSION: In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.

Randomized clinical trial assessing the safety and immunogenicity of oral microencapsulated enterotoxigenic Escherichia coli surface antigen 6 with or without heat-labile enterotoxin with mutation R192G.

An oral, microencapsulated anti-colonization factor 6 antigen (meCS6) vaccine, with or without heat-labile enterotoxin with mutation R192G (LT(R192G)) (mucosal adjuvant), against enterotoxigenic Escherichia coli (ETEC) was evaluated for regimen and adjuvant effects on safety and immunogenicity. Sixty subjects were enrolled into a three-dose, 2-week interval or four-dose, 2-day interval regimen. Each regimen was randomized into two equal groups of meCS6 alone (1 mg) or meCS6 with adjuvant (2 microg of LT(R192G)). The vaccine was well tolerated and no serious adverse events were reported. Serologic response to CS6 was low in all regimens (0 to 27%). CS6-immunoglobulin A (IgA) antibody-secreting cell (ASC) responses ranged from 36 to 86%, with the highest level in the three-dose adjuvanted regimen; however, the magnitude was low. As expected, serologic and ASC LT responses were limited to adjuvanted regimens, with the exception of fecal IgA, which appeared to be nonspecific to LT administration. Further modifications to the delivery strategy and CS6 and adjuvant dose optimization will be needed before conducting further clinical trials with this epidemiologically important class of ETEC.

Analysis of cases reported as generalized vaccinia during the US military smallpox vaccination program, December 2002 to December 2004.

BACKGROUND: We evaluated military personnel who developed dermatologic reactions suggestive of generalized vaccinia (GV) after smallpox vaccination. METHODS: We conducted surveillance and retrospective analysis of cases from the Vaccine Adverse Event Reporting System (a passive reporting system managed by the Centers for Disease Control and Prevention), and the military's preventive medicine channels, vaccine healthcare centers, clinical laboratory network, dermatology clinics, and pathology departments from December 2002 to December 2004. RESULTS: Of 74 cases investigated in 753,226 vaccinations, 50 (67.6%) met the case definition of possible GV (rate 66/million), 95% confidence interval (49-88/million), consistent with historically reported rates. Cases of possible GV occurred more frequently in primary vaccinees (81/million) than in those revaccinated (32/million) (relative risk 2.6, 95% confidence interval 1.2-5.9, P = .013). None met the case definition of probable or confirmed GV, including 15 with virologically negative laboratory evaluations (eg, culture, skin biopsy, or polymerase chain reaction). LIMITATIONS: The methods of case collection and retrospective nature of this study are its limitations. The clinical diagnosis of possible GV was made on the basis of the authors' interpretation of clinical notes and adverse events submitted by more than 100 different providers. Only 15 of the 74 cases of possible GV had laboratory attempts for virological confirmation. CONCLUSION: GV is still a rarely reported complication of smallpox vaccination. True GV, strictly defined, may be even less common than previously reported. We named one self-limited dermatologic manifestation confused with GV "postvaccinial nonviral pustulosis." Properly screened individuals considering smallpox vaccination may be assured most exanthemata after vaccination are benign.