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A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

Sayeed MA, Bufano MK, Xu P, Eckhoff G, Charles RC, Alam MM, Sultana T, Rashu MR, Berger A, Gonzalez-Escobedo G, Mandlik A, Bhuiyan TR, Leung DT, LaRocque RC, Harris JB, Calderwood SB, Qadri F, Vann WF, Kováč P, Ryan ET - PLoS Negl Trop Dis (2015)

Bottom Line: Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination.We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum.Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.

ABSTRACT

Background: Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).

Methodology: Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.

Principle findings: Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.

Conclusion: We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

No MeSH data available.


Related in: MedlinePlus

Immunoreactivity in human plasma of OSP:rTTHc, OSP:BSA, and TT.Immunoreactivity of OSP:rTTHc, OSP:BSA and TT was measured in day 2 versus day 7 plasma of patients with cholera versus typhoid fever in Dhaka, Bangladesh.
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pntd.0003881.g002: Immunoreactivity in human plasma of OSP:rTTHc, OSP:BSA, and TT.Immunoreactivity of OSP:rTTHc, OSP:BSA and TT was measured in day 2 versus day 7 plasma of patients with cholera versus typhoid fever in Dhaka, Bangladesh.

Mentions: To assess whether the conjugates displayed OSP in a immunologically relevant manner, we assessed immunoreactivity of OSP:rTTHc (Fig 1) and OSP:BSA using sera from humans with cholera or typhoid in Bangladesh. We found a significant increase in immunoreactivity to these conjugates in humans recovering from cholera, but not typhoid (Fig 2). As expected, we found no change in antibody levels to tetanus toxoid during the course of clinical illness in either group of patients.


A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

Sayeed MA, Bufano MK, Xu P, Eckhoff G, Charles RC, Alam MM, Sultana T, Rashu MR, Berger A, Gonzalez-Escobedo G, Mandlik A, Bhuiyan TR, Leung DT, LaRocque RC, Harris JB, Calderwood SB, Qadri F, Vann WF, Kováč P, Ryan ET - PLoS Negl Trop Dis (2015)

Immunoreactivity in human plasma of OSP:rTTHc, OSP:BSA, and TT.Immunoreactivity of OSP:rTTHc, OSP:BSA and TT was measured in day 2 versus day 7 plasma of patients with cholera versus typhoid fever in Dhaka, Bangladesh.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495926&req=5

pntd.0003881.g002: Immunoreactivity in human plasma of OSP:rTTHc, OSP:BSA, and TT.Immunoreactivity of OSP:rTTHc, OSP:BSA and TT was measured in day 2 versus day 7 plasma of patients with cholera versus typhoid fever in Dhaka, Bangladesh.
Mentions: To assess whether the conjugates displayed OSP in a immunologically relevant manner, we assessed immunoreactivity of OSP:rTTHc (Fig 1) and OSP:BSA using sera from humans with cholera or typhoid in Bangladesh. We found a significant increase in immunoreactivity to these conjugates in humans recovering from cholera, but not typhoid (Fig 2). As expected, we found no change in antibody levels to tetanus toxoid during the course of clinical illness in either group of patients.

Bottom Line: Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination.We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum.Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.

ABSTRACT

Background: Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).

Methodology: Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.

Principle findings: Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.

Conclusion: We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

No MeSH data available.


Related in: MedlinePlus