Production of IgG2 Antibodies to Pneumococcal Polysaccharides After Vaccination of Treated HIV Patients May Be Augmented by IL-7Rα Signaling in ICOS+ Circulating T Follicular-Helper Cells.

Laila N Abudulai,Martyn A French,Karli Corscadden,Jeffrey J Post,Michael Hunter,Sonia Fernandez,Lea-Ann Kirkham

doi:10.3389/fimmu.2019.00839

Abstract

Greater understanding of factors influencing the maturation of antibody responses against pneumococcal polysaccharides (PcPs) may improve pneumococcal vaccination strategies. Although PcPs are type 2 T cell-independent antigens thought not to induce follicular immune responses, we have previously shown that IgG2 antibody responses against antigens in the 23-valent unconjugated PcP vaccine (PPV23) are associated with expansion of ICOS+ circulating T follicular helper (cTFH) cells in HIV seronegative subjects but not HIV patients. As IL-7Rα signaling in CD4+ T cells may affect TFH cell function and is adversely affected by HIV-1 infection, we have examined the relationship of IL-7Rα expression on ICOS+ cTFH cells with PcP-specific IgG2 antibody responses. PPV23 vaccination was undertaken in HIV patients receiving antiretroviral therapy (n = 25) and HIV seronegative subjects (n = 20). IL-7Rα expression on ICOS+ and ICOS− cTFH cells was assessed at day(D) 0, 7, and 28. Fold increase between D0 and D28 in serum IgG1 and IgG2 antibodies to PcP serotypes 4, 6B, 9V, and 14 and the frequency of IgG1+ and IgG2+ antibody secreting cells (ASCs) at D7 were also assessed. Decline in IL-7Rα expression on ICOS+ cTFH cells between D0 and D7 occurred in 75% of HIV seronegative subjects and 60% of HIV patients (Group A), with changes in IL-7Rα expression being more pronounced in HIV patients. Group A patients exhibited abnormally high IL-7Rα expression pre-vaccination, an association of serum IgG2, but not IgG1, antibody responses with a decline of IL-7Rα expression on ICOS+ cTFH cells between D0 and D7, and an association of higher IgG2+ ASCs with lower IL-7Rα expression on ICOS+ cTFH cells at D7. As decline of IL-7Rα expression on CD4+ T cells is an indicator of IL-7Rα signaling, our findings suggest that utilization of IL-7 by cTFH cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients.

Highlights

The immunogenicity of pneumococcal vaccines is increased by protein conjugation of pneumococcal polysaccharides (PcPs), leading to recruitment of T cell “help” [1], strategies for enhancing IgG antibody production and the generation of memory B cells (MBCs) are still needed
We have demonstrated that 75% of human immunodeficiency virus (HIV) seronegative subjects and 60% of antiretroviral therapy (ART)-treated HIV patients exhibited a decline in IL-7Rα expression on inducible co-stimulator (ICOS)+ circulating T follicular helper (cTFH) cells, the activated subpopulation of cTFH cells [15, 16], between D0 and D7 of vaccination with PPV23
Amongst HIV patients who exhibited a decline in IL7Rα expression on ICOS+ cTFH cells (Group A), a greater decline in IL-7Rα expression on ICOS+ cTFH cells between D0 and D7 was associated with higher serum IgG2 but not IgG1 PcP-specific antibody responses

Summary

Introduction

The immunogenicity of pneumococcal vaccines is increased by protein conjugation of pneumococcal polysaccharides (PcPs), leading to recruitment of T cell “help” [1], strategies for enhancing IgG antibody production and the generation of memory B cells (MBCs) are still needed. This is so for people at greatest risk of pneumococcal disease, including patients with human immunodeficiency virus (HIV) infection treated with antiretroviral therapy (ART). T cell-independent antibody responses consist predominantly of IgM antibodies and, vaccination with PcPs induces predominantly IgM+ memory B cells (MBCs) [6]. IgG2 deficiency is associated with an increased susceptibility to infections of the respiratory tract by encapsulated bacteria, including pneumococci [8, 9]

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Conclusion