Leggat David J, Iyer Anita S, Ohtola Jennifer A, Kommoori Sneha, Duggan Joan M, Georgescu Claudiu A, Khuder Sadik A, Khaskhely Noor M, Westerink Ma Julie
Department of Medicine, University of Toledo, USA.
Department of Medicine, University of Toledo, USA ; Department of Medical Microbiology and Immunology, University of Toledo, USA ; Department of Internal Medicine, University of Toledo, USA ; Department of Pathology, University of Toledo, USA ; Department of Physiology, University of Toledo, USA ; Department of Pharmacology, University of Toledo, USA ; Department of Metabolism & Cardiovascular Science, University of Toledo, USA.
J AIDS Clin Res. 2015 Feb;6(2). doi: 10.4172/2155-6113.1000419.
Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible to infection compared to non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature of HIV infection. The specific nature of the immune cells involved in the production of protective antigen-specific antibodies in HIV-positive individuals remains to be elucidated.
Evaluate the antibody and antigen-specific B cell response to the 23-valent pneumococcal polysaccharide vaccine in newly diagnosed HIV-positive patients. Moreover, determine if newly diagnosed patients with CD4<200 cells/μl benefit from 6-12 months of HAART, allowing partial viral suppression and immune reconstitution, prior to immunization.
Newly diagnosed HIV-positive patients with CD4>200 cells/μl and CD4<200 cells/μl were immunized with PPV23. Patients with CD4<200 cells/μl received either immediate or delayed immunization following 6-12 months of HAART. Antibody responses, opsonophagocytic activity and phenotypic analysis of pneumococcal polysaccharide-specific B cells were studied.
Newly diagnosed HIV-positive patients demonstrated CD4-dependent increases in antibody and opsonophagocytic titers thought to be commensurate with protection. Functional opsonophagocytic titers of patients with CD4<200 cells/μl immunized immediately compared to patients with CD4<200 cells/μl receiving HAART for 6-12 months were not significantly different. Pneumococcal polysaccharide-specific B cells were distributed evenly between IgM memory and switched memory B cells for all groups, but IgM memory B cells were significantly lower than in HIV-negative individuals.
Despite CD4-dependent pneumococcal polysaccharide-specific deficiencies in newly diagnosed HIV-positive patients, vaccination was beneficial based on opsonophagocytic titers for all newly diagnosed HIV-positive groups. In HIV-positive patients with CD4<200 cells/μl, 6-12 months of HAART did not improve opsonophagocytic titers or antibody concentrations. Based on these findings, immunization with the 23-valent pneumococcal polysaccharide vaccine should not be delayed in newly diagnosed HIV-positive patients with CD4<200 cells/μl.
新诊断出的HIV阳性个体比未感染个体更易感染35至100倍。因此，之前推荐使用23价肺炎球菌多糖疫苗（PPV23），尽管疫苗接种的疗效和有效性仍存在争议。早期严重的B细胞功能障碍是HIV感染的核心特征。HIV阳性个体中参与产生保护性抗原特异性抗体的免疫细胞的具体性质仍有待阐明。
评估新诊断出的HIV阳性患者对23价肺炎球菌多糖疫苗的抗体和抗原特异性B细胞反应。此外，确定新诊断出的CD4<200细胞/μl的患者在免疫接种前接受6至12个月的高效抗逆转录病毒治疗（HAART），实现部分病毒抑制和免疫重建是否有益。
对新诊断出的CD4>200细胞/μl和CD4<200细胞/μl的HIV阳性患者接种PPV23。CD4<200细胞/μl的患者在接受6至12个月的HAART后立即或延迟接种。研究了抗体反应、调理吞噬活性以及肺炎球菌多糖特异性B细胞的表型分析。
新诊断出的HIV阳性患者表现出与保护作用相当的抗体和调理吞噬滴度的CD4依赖性增加。与接受6至12个月HAART的CD4<200细胞/μl患者相比，立即接种的CD4<200细胞/μl患者的功能性调理吞噬滴度无显著差异。所有组的肺炎球菌多糖特异性B细胞在IgM记忆B细胞和转换记忆B细胞之间均匀分布，但IgM记忆B细胞显著低于HIV阴性个体。
尽管新诊断出的HIV阳性患者存在CD4依赖性肺炎球菌多糖特异性缺陷，但基于所有新诊断出的HIV阳性组的调理吞噬滴度，疫苗接种是有益的。在CD4<200细胞/μl的HIV阳性患者中，6至12个月的HAART并未提高调理吞噬滴度或抗体浓度。基于这些发现，对于新诊断出的CD4<200细胞/μl的HIV阳性患者，不应延迟接种23价肺炎球菌多糖疫苗。
