Incomplete Correlation of Serum Vibriocidal Antibody Titer with Protection from<i>Vibrio cholerae</i>Infection in Urban Bangladesh

Saha, Debasish; LaRocque, Regina C.; Khan, Ashraful Islam; Harris, Jason B.; Begum, Yasmin; Akramuzzaman, Syed M.; Faruque, A. S. G.; Ryan, Edward T.; Qadri, Firdausi; Calderwood, Stephen B.

doi:10.1086/421275

Cited by 92 publications

(93 citation statements)

References 15 publications

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“…We have an ongoing study in Bangladesh of patients hospitalized with cholera and their household contacts (27). Some of the household contacts develop symptomatic cholera, some are asymptomatically colonized, and some are not infected.…”

Section: Discussionmentioning

confidence: 99%

The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139

et al. 2004

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Diarrhea caused by Vibrio cholerae is known to give long-lasting protection against subsequent life-threatening illness. The serum vibriocidal antibody response has been well studied and has been shown to correlate with protection. However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxin-coregulated pilus (TCP) and other factors. Information regarding immune responses to TCP, particularly mucosal immune responses, is lacking, particularly for patients infected with the El Tor biotype of V. cholerae O1 or V. cholerae O139 since highly purified TcpA from these strains has not been available previously for use in immune assays. We studied the immune responses to El Tor TcpA in cholera patients in Bangladesh. Patients had substantial and significant increases in TcpA-specific antibody-secreting cells in the circulation on day 7 after the onset of illness, as well as similar mucosal responses as determined by an alternate technique, the assay for antibody in lymphocyte supernatant. Significant increases in antibodies to TcpA were also seen in sera and feces of patients on days 7 and 21 after the onset of infection. Overall, 93% of the patients showed a TcpA-specific response in at least one of the specimens compared with the results obtained on day 2 and with healthy controls. These results demonstrate that TcpA is immunogenic following natural V. cholerae infection and suggest that immune responses to this antigen should be evaluated for potential protection against subsequent life-threatening illness.Diarrhea caused by Vibrio cholerae is known to give longlasting protection against subsequent life-threatening illness (2, 3, 15). The serum vibriocidal antibody response has been well studied and has been shown to be correlated with protection (8,16,17,18). However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxincoregulated pilus (TCP). TCP is essential for V. cholerae colonization of the small intestine both in an infant mouse model of cholera (28) and during human infection (11). The gene encoding the major pilin subunit, TcpA, is located within a larger genetic element termed the Vibrio pathogenicity island or TCP/ACF element (7, 19). Although TcpA is expressed by both classical and El Tor biotypes of V. cholerae O1, as well as by V. cholerae O139, there is only 80% amino acid identity between the TcpA proteins of the two biotypes of V. cholerae O1 (12, 13, 28). TcpA of El Tor V. cholerae O1 and TcpA of V. cholerae O139 are identical (25).In previous studies of the immune responses to TcpA in patients with V. cholerae infections the workers have examined patients infected with the classical biotype of V. cholerae O1 or have utilized classical TcpA to assess immune responses in patients infected with El Tor V. cholerae O1 (9). Recent studies in which the in vivo-induced antigen technology has been used have shown ...

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Section: Discussionmentioning

confidence: 99%

The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139

et al. 2004

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“…However, there is no threshold level of vibriocidal titer that confers complete protection from infection or symptoms, and the vibriocidal antibody is thought to be a surrogate marker of a protective mucosal immune response. [7][8][9][10] In areas where cholera is endemic, most residents have detectable vibriocidal antibodies by the teenage years, and titers increase with age. 10,11 Because of the background rate of vibriocidal antibodies in these populations, there is no threshold cutoff diagnostic of infection in an endemic area.…”

Section: Introductionmentioning

confidence: 99%

Frequency of Reexposure to Vibrio cholerae O1 Evaluated by Subsequent Vibriocidal Titer Rise after an Episode of Severe Cholera in a Highly Endemic Area in Bangladesh

Weil¹,

Chowdhury²,

Khan³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Vibriocidal antibody is a marker of recent exposure to Vibrio cholerae O1 infection. We examined vibriocidal titers for 1 year after an episode of severe cholera in patients in Dhaka, Bangladesh; 16 of 53 (30%) patients had a fourfold or greater increase in vibriocidal titer between 6 and 12 months after an episode of severe cholera, suggesting reexposure to the organism. Among patients with rises in titers during follow-up, the patients initially infected with serotype Ogawa had earlier rises in titer than the patients initially infected with serotype Inaba. These data and others suggest that an episode of severe cholera protects against symptomatic disease for several years, but reexposure to the organism occurs frequently in an endemic area, with immunological boosts beginning as early as 6 months after severe disease. Repeated exposures to V. cholerae in endemic areas may be a necessary component for long-lasting protection against severe disease.

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“…The immunologic mechanism of protection against cholera is currently unknown, although available evidence suggests it probably involves anti-LPS responses, as described above. Vibriocidal responses are often used to predict protection, but this complement-binding serum-based assay is presumably a surrogate marker of protection, since V. cholerae is a noninvasive luminal pathogen, there is no known vibriocidal titer above which protection is complete (28), and vibriocidal antibody levels fall to baseline within several months after infection (8). Similarly, serum and mucosal anti-V. cholerae antibody responses fall to baseline within months of infection, despite the presence of ongoing protection from disease (8).…”

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Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera

Alam

Riyadh

Fatema

et al. 2011

Clin. Vaccine Immunol.

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Incomplete Correlation of Serum Vibriocidal Antibody Titer with Protection fromVibrio choleraeInfection in Urban Bangladesh

Cited by 92 publications

References 15 publications

The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139

The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139

Frequency of Reexposure to Vibrio cholerae O1 Evaluated by Subsequent Vibriocidal Titer Rise after an Episode of Severe Cholera in a Highly Endemic Area in Bangladesh

Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera

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