APRIL:TACI axis is dispensable for the immune response to rabies vaccination.
APRIL:TACI axis is dispensable for the immune response to rabies vaccination.
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DOI：
10.1016/j.antiviral.2017.06.004
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发表时间：
2017-08
影响因子：
7.6
通讯作者：
McGettigan JP
中科院分区：
文献类型：
--
作者：
Haley SL;Tzvetkov EP;Lytle AG;Alugupalli KR;Plummer JR;McGettigan JP
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)–expressed by B cells in various stages of maturation–with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination.
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影响因子：
3.8
作者：
Dorfmeier CL;Tzvetkov EP;Gatt A;McGettigan JP
通讯作者：
McGettigan JP
影响因子：
5.4
作者：
McGettigan, JP;Naper, K;Schnell, MJ
通讯作者：
Schnell, MJ
影响因子：
5.4
作者：
McGettigan, JP;Sarma, S;Schnell, MJ
通讯作者：
Schnell, MJ
影响因子：
6.2
作者：
McGettigan JP
通讯作者：
McGettigan JP
影响因子：
32.4
作者：
He, Bing;Xu, Weifeng;Cerutti, Andrea
通讯作者：
Cerutti, Andrea