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.
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...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS Neglected Tropical Diseases |
Online Access: | http://europepmc.org/articles/PMC4495926?pdf=render |
id |
doaj-0e79629c217d48a793da67a0f610ed0b |
---|---|
record_format |
Article |
spelling |
doaj-0e79629c217d48a793da67a0f610ed0b2020-11-25T00:15:14ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-01-0197e000388110.1371/journal.pntd.0003881A 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.Md Abu SayeedMeagan Kelly BufanoPeng XuGrace EckhoffRichelle C CharlesMohammad Murshid AlamTania SultanaMd Rasheduzzaman RashuAmanda BergerGeoffrey Gonzalez-EscobedoAnjali MandlikTaufiqur Rahman BhuiyanDaniel T LeungRegina C LaRocqueJason B HarrisStephen B CalderwoodFirdausi QadriW F VannPavol KováčEdward T RyanBACKGROUND: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.http://europepmc.org/articles/PMC4495926?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Md Abu Sayeed Meagan Kelly Bufano Peng Xu Grace Eckhoff Richelle C Charles Mohammad Murshid Alam Tania Sultana Md Rasheduzzaman Rashu Amanda Berger Geoffrey Gonzalez-Escobedo Anjali Mandlik Taufiqur Rahman Bhuiyan Daniel T Leung Regina C LaRocque Jason B Harris Stephen B Calderwood Firdausi Qadri W F Vann Pavol Kováč Edward T Ryan |
spellingShingle |
Md Abu Sayeed Meagan Kelly Bufano Peng Xu Grace Eckhoff Richelle C Charles Mohammad Murshid Alam Tania Sultana Md Rasheduzzaman Rashu Amanda Berger Geoffrey Gonzalez-Escobedo Anjali Mandlik Taufiqur Rahman Bhuiyan Daniel T Leung Regina C LaRocque Jason B Harris Stephen B Calderwood Firdausi Qadri W F Vann Pavol Kováč Edward T Ryan 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. PLoS Neglected Tropical Diseases |
author_facet |
Md Abu Sayeed Meagan Kelly Bufano Peng Xu Grace Eckhoff Richelle C Charles Mohammad Murshid Alam Tania Sultana Md Rasheduzzaman Rashu Amanda Berger Geoffrey Gonzalez-Escobedo Anjali Mandlik Taufiqur Rahman Bhuiyan Daniel T Leung Regina C LaRocque Jason B Harris Stephen B Calderwood Firdausi Qadri W F Vann Pavol Kováč Edward T Ryan |
author_sort |
Md Abu Sayeed |
title |
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. |
title_short |
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. |
title_full |
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. |
title_fullStr |
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. |
title_full_unstemmed |
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. |
title_sort |
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. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4495926?pdf=render |
work_keys_str_mv |
AT mdabusayeed acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT meagankellybufano acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT pengxu acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT graceeckhoff acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT richelleccharles acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT mohammadmurshidalam acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT taniasultana acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT mdrasheduzzamanrashu acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT amandaberger acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT geoffreygonzalezescobedo acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT anjalimandlik acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT taufiqurrahmanbhuiyan acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT danieltleung acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT reginaclarocque acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT jasonbharris acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT stephenbcalderwood acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT firdausiqadri acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT wfvann acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT pavolkovac acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT edwardtryan acholeraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT mdabusayeed choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT meagankellybufano choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT pengxu choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT graceeckhoff choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT richelleccharles choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT mohammadmurshidalam choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT taniasultana choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT mdrasheduzzamanrashu choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT amandaberger choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT geoffreygonzalezescobedo choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT anjalimandlik choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT taufiqurrahmanbhuiyan choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT danieltleung choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT reginaclarocque choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT jasonbharris choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT stephenbcalderwood choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT firdausiqadri choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT wfvann choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT pavolkovac choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice AT edwardtryan choleraconjugatevaccinecontainingospecificpolysaccharideospofvcholeraeo1inabaandrecombinantfragmentoftetanustoxinheavychainosprtthcinducesserummemoryandlaminaproprialresponsesagainstospandisprotectiveinmice |
_version_ |
1725387914719789056 |