Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

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• 作者：Zhenwu Luo^a ; ¹ ; Lei Ma^b ; ¹ ; Lumin Zhang^a ; Lisa Martin^c ; Zhuang Wan^d ; Stephanie Warth^c ; Andrew Kilby^c ; Yong Gao^e ; Pallavi Bhargava^f ; Zhen Li^g ; Hao Wu^g ; Eric G. Meissner^c ; Zihai Li^a ; J. Michael Kilby^c ; Guoyang Liao^b ; ^{liaogy@imbcams.com.cn" class="auth_mail" title="E-mail the corresponding author} ; Wei Jiang^a ; ^c ; ^{jianw@musc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HIV disease ; B cells ; Antibody responses ; Influenza vaccine
• 刊名：Vaccine
• 出版年：2016
• 出版时间：7 April 2016
• 年：2016
• 卷：34
• 期：16
• 页码：1945-1955
• 全文大小：2876 K

文摘

There is increasing recognition of the role of B cell dysfunction in HIV pathogenesis, but little is known about how these perturbations may influence responses to vaccinations.

Methods

Healthy controls (n = 16) and antiretroviral therapy (ART)-treated aviremic HIV-infected subjects (n = 26) receiving standard-of-care annual influenza vaccinations were enrolled in the present study. Total bacterial 16 S rDNA levels were assessed by quantitative polymerase chain reactions in plasma. Serologic responses were characterized by ELISA, hemagglutination inhibition assay (HI), and microneutralization, and cell-mediated responses were assessed by ELISPOT (antigen-specific IgG+ antibody-secreting cells (ASCs)) and flow cytometry at pre-vaccination (D0), day 7–10 (D7) and day 14–21 (D14) post-vaccination.

Results

Decreased peripheral CD4+ T cell absolute counts and increased frequencies of cycling and apoptotic B cells were found at baseline in HIV-infected subjects relative to healthy controls. In healthy controls, post-vaccination neutralizing activities were related to the frequencies of vaccine-mediated apoptosis and cycling of B cells, but not to CD4+ T cell counts. In patients, both baseline and post-vaccination neutralizing activities were directly correlated with plasma level of bacterial 16S rDNA. However, overall vaccine responses including antibody titers and fold changes were comparable or greater in HIV-infected subjects relative to healthy controls.

Conclusion

B cell function correlates with measures of recall humoral immunity in response to seasonal influenza vaccination in healthy controls but not in ART-treated patients.