CD40 antibody as a potent immunological adjuvant: CD40 antibody provides the CD40 signal to B cells, but does not substitute for T cell help in responses to TD antigens

Barr, Tom A.; Carlring, Jennifer; Heath, Andrew W.

doi:10.1016/j.vaccine.2004.12.025

Cited by 21 publications

(21 citation statements)

References 23 publications

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“…An important observation of our studies is that the treatment of vaccinated CD154 Ϫ/Ϫ mice with antiCD40 MAb did not restore anti-parasite antibody production, in agreement with a study on allograft immunity (50), although other studies demonstrate that anti-CD40 MAb can restore antibody isotype class switching (4,63). The administration of rIL-12 also did not restore antibody production in vaccinated CD154…”

Section: Discussionsupporting

confidence: 89%

In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity toSchistosoma mansoni

2007

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The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154 ؊/؊ mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154 ؊/؊ mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154 ؊/؊ mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154 ؊/؊ mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154 ؊/؊ mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c؉ cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154 ؊/؊ mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs.

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Section: Discussionsupporting

confidence: 89%

In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity toSchistosoma mansoni

2007

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“…Agonistic antibodies against CD40 have great potential as immunological adjuvants to induce strong antibody responses against conjugated antigen [372,373]. It is believed that the adjuvant effect is mediated at least in part through enhanced antigen presentation by specific B cells [373].…”

Section: Specific Peptides/proteinsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…Immunogens and/or immunization regimes that can selectively activate CD40L-CD40 but not CD28-CD80/CD86 costimulatory signaling pathways may be chosen to induce better protection against chlamydial infection and Chlamydia-induced diseases. In fact, activation of CD40 has been evaluated as an adjuvant strategy to enhance vaccine immunogenicity (3,5). …”

Section: Vol 77 2009 Cd28 and Cd40l In C Muridarum Urogenital Infementioning

confidence: 99%

Distinct Roles of CD28- and CD40 Ligand-Mediated Costimulation in the Development of Protective Immunity and Pathology duringChlamydia muridarumUrogenital Infection in Mice

Chen

Cheng

Shivshankar³

et al. 2009

Infect Immun

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Infection with Chlamydia muridarum in the mouse urogenital tract can induce both protective immunity and inflammatory pathologies, which has been used as a model for understanding the immune and pathogenic mechanisms of C. trachomatis infection. We compared the roles of CD28-and CD40 ligand (CD40L)-mediated costimulation in C. muridarum infection. Mice with CD28 or CD80/CD86 gene knockout (KO) displayed an infection course similar to that of wild-type mice during both primary and secondary infection, suggesting that CD28-mediated costimulation is not required for protection against C. muridarum infection. However, mice deficient in CD40L or CD40 displayed a prolonged infection course after primary or secondary infection, suggesting that CD40-CD40L costimulation plays an essential role in the development of anti-C. muridarum immunity. Interestingly, the CD28-or CD80/CD86-deficient mice displayed significantly lower levels of inflammatory pathologies in the upper genital tracts after primary infection, although the attenuation in inflammation was no longer significant during secondary infection. However, the CD40L or CD40 KO mice developed inflammatory pathologies as severe as those in wild-type mice following either primary or secondary infection despite the obvious deficits in adaptive immunity in these KO mice. The resistance of CD28 or CD80/CD86 KO mice to chlamydial infection correlated with production of gamma interferon, while the development of inflammatory pathologies in CD40L or CD40 KO mice correlated with the production of other proinflammatory cytokines in mouse urogenital tracts during the early stages of the infection. These observations together suggest that C. muridarum-induced protective immunity and inflammatory pathologies can be mediated by distinct costimulatory signals.

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CD40 antibody as a potent immunological adjuvant: CD40 antibody provides the CD40 signal to B cells, but does not substitute for T cell help in responses to TD antigens

Cited by 21 publications

References 23 publications

In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity toSchistosoma mansoni

In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity toSchistosoma mansoni

Selection of Adjuvants for Enhanced Vaccine Potency

Distinct Roles of CD28- and CD40 Ligand-Mediated Costimulation in the Development of Protective Immunity and Pathology duringChlamydia muridarumUrogenital Infection in Mice

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