Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine

Oral cholera vaccination protects against cholera; however, responses in young children are low and of short duration. The best current correlates of protection against cholera target Vibrio cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A cholera conjugate vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether cholera conjugate vaccine would boost immune responses following oral cholera vaccination, we immunized mice with oral cholera vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with cholera conjugate vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or PBS/placebo. Compared with responses in mice immunized with oral vaccine alone or intramuscular cholera conjugate vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral cholera vaccination followed by parenteral cholera conjugate vaccine boosting, results in increased immune responses that have been associated with protection against cholera. These results suggest that such an approach should be evaluated in humans.

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Affinity Enhancement of Antibodies: How Low-Affinity Antibodies Produced Early in Immune Responses Are Followed by High-Affinity Antibodies Later and in Memory B-Cell Responses

Cancer Immunology Research ◽

10.1158/2326-6066.cir-14-0029 ◽

2014 ◽

Vol 2 (5) ◽

pp. 381-392 ◽

Cited By ~ 65

Author(s):

Herman N. Eisen

Keyword(s):

Immune Responses ◽

B Cell ◽

Memory B Cell ◽

Cell Responses ◽

High Affinity ◽

B Cell Responses

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Correction: The Magnitude of the Antibody and Memory B Cell Responses during Priming with a Protein-Polysaccharide Conjugate Vaccine in Human Infants Is Associated with the Persistence of Antibody and the Intensity of Boster Response

The Journal of Immunology ◽

10.4049/jimmunol.1190012 ◽

2011 ◽

Vol 186 (10) ◽

pp. 6064-6064

Author(s):

Geraldine Blanchard Rohner ◽

Matthew D. Snape ◽

Dominic F. Kelly ◽

Tessa John ◽

Anita Morant ◽

...

Keyword(s):

B Cell ◽

Conjugate Vaccine ◽

Human Infants ◽

Memory B Cell ◽

Cell Responses ◽

B Cell Responses

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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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00562-10 ◽

2011 ◽

Vol 18 (5) ◽

pp. 844-850 ◽

Cited By ~ 52

Author(s):

Mohammad Murshid Alam ◽

M. Asrafuzzaman Riyadh ◽

Kaniz Fatema ◽

Mohammad Arif Rahman ◽

Nayeema Akhtar ◽

...

Keyword(s):

B Cell ◽

Acute Stage ◽

Cholera Toxin B Subunit ◽

Memory B Cell ◽

Content Type ◽

Cell Responses ◽

Specific Memory ◽

Dose Oral ◽

B Cell Responses ◽

Cholera Vaccination

ABSTRACTThe mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses againstVibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n= 70) to responses in Bangladeshi adults after one-dose (n= 30) or two-dose (n= 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease.

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Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Clinical and Vaccine Immunology ◽

10.1128/cvi.05615-11 ◽

2012 ◽

Vol 19 (5) ◽

pp. 690-698 ◽

Cited By ~ 30

Author(s):

Daniel T. Leung ◽

Mohammad Arif Rahman ◽

M. Mohasin ◽

Sweta M. Patel ◽

Amena Aktar ◽

...

Keyword(s):

Young Children ◽

Immune Responses ◽

B Cell ◽

Protective Efficacy ◽

Cholera Toxin B Subunit ◽

Cholera Vaccine ◽

Wild Type ◽

Memory B Cell ◽

Content Type ◽

Cholera Vaccination

ABSTRACTCurrent oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age;n= 20) and older children (6 to 17 years of age;n= 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection withVibrio choleraeO1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.

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Persistence of antibody and T cell responses to the Sinopharm/BBIBP-CorV vaccine in Sri Lankan individuals

10.1101/2021.10.14.21265030 ◽

2021 ◽

Author(s):

Chandima Jeewandara ◽

Inoka Aberathna ◽

Pradeep Pushpakumara ◽

Achala Kamaladasa ◽

Dinuka Guruge ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

B Cell ◽

Severe Disease ◽

Age Groups ◽

T Cell Responses ◽

Sri Lankan ◽

Memory B Cell ◽

Cell Responses ◽

B Cell Responses

Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods: SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second dose of the vaccine. ACE2 receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. Results: 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. 14.3% to 16.7% individuals in the 20 to 39 age groups had detectable antibodies to the RBD of the WT and VOC, while the positivity rates of those >60 years of age was <10%. 14/49 (28.6%) had IFNγ ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined after 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40 to 59 (p=0.0007) and ≥60 (p=0.005) age groups. Conclusions: Antibody responses declined in all age groups, especially in those >60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.

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