The success of an HIV vaccine will require induction of a protective immune response in the most at-risk populations. The increased incidence of HIV infection in high-risk populations is assumed to be primarily the result of more frequent exposure to the virus or a greater inoculum of the virus; however, underlying variations in immune homeostasis may also contribute to HIV susceptibility and potentially impact vaccine responses and those required for protection. As an effective humoral immune response is likely to be a critical component of a protective HIV vaccine, we evaluated the steady-state phenotypic profile of peripheral blood B cells by flow cytometry from participants in the HIV Vaccine Trials Network (HVTN) 203 Phase 2a HIV vaccine trial considered to be at higher risk and lower risk for HIV acquisition. Overall, high-risk participants exhibited increased frequency of unswitched IgM memory and activated switched IgD−CD95+ memory B cells than low-risk participants. Most (93%) of the high-risk male participants were men who have sex with men who engaged in high-risk sexual behavior. High-risk males had a significantly increased frequency of CXCR3+ IgD−CD95+ B cells than low-risk males. These results suggest that high-risk populations have altered B cell homeostasis. The increased frequency of activated and memory B cells may suggest increased immune activation in high-risk populations, which may contribute to possible differential responses to HIV vaccine strategies.
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References
1.
Rerks-NgarmS, PitisuttithumP, NitayaphanS, et al.: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med, 2009; 361:2209–2220.
2.
SchiffnerT, SattentauQJ, DorrellL: Development of prophylactic vaccines against HIV-1. Retrovirology, 2013; 10:72.
3.
PalmerCD, TomassilliJ, SirignanoM, et al.: Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM. AIDS, 2014; 28:2162–2166.
4.
HeiligenbergM, LutterR, PajkrtD, et al.: Effect of HIV and chlamydia infection on rectal inflammation and cytokine concentrations in men who have sex with men. Clin Vaccine Immunol, 2013; 20:1517–1523.
5.
TomescuC, SeatonKE, SmithP, et al.: Innate activation of MDC and NK cells in high-risk HIV-1-exposed seronegative IV-drug users who share needles when compared with low-risk nonsharing IV-drug user controls. J Acquir Immune Defic Syndr, 2015; 68:264–273.
6.
TomescuC, DuhFM, LanierMA, et al.: Increased plasmacytoid dendritic cell maturation and natural killer cell activation in HIV-1 exposed, uninfected intravenous drug users. AIDS, 2010; 24:2151–2160.
YatesNL, LiaoHX, FongY, et al.: Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med, 2014; 6:228ra239.
9.
ChungAW, KumarMP, ArnoldKB, et al.: Dissecting polyclonal vaccine-induced humoral immunity against HIV using systems serology. Cell, 2015; 163:988–998.
10.
RussellND, GrahamBS, KeeferMC, et al.: Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: Negative results fail to trigger a phase 3 correlates trial. J Acquir Immune Defic Syndr, 2007; 44:203–212.
11.
KobieJJ, AlcenaDC, ZhengB, et al.: 9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity. PLoS One, 2012; 7:e35356.
12.
KobieJJ, ZhengB, BrykP, et al.: Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor. Arthritis Res Ther, 2011; 13:R209.
13.
HallileyJL, KyuS, KobieJJ, et al.: Peak frequencies of circulating human influenza-specific antibody secreting cells correlate with serum antibody response after immunization. Vaccine, 2010; 28:3582–3587.
14.
QianY, WeiC, Eun-Hyung LeeF, et al.: Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data. Cytometry B Clin Cytom, 2010; 78Suppl 1:S69–S82.
15.
GalsonJD, TruckJ, FowlerA, et al.: Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences. EBioMedicine, 2015; 2:2070–2079.
16.
CapolunghiF, RosadoMM, SinibaldiM, AranburuA, CarsettiR: Why do we need IgM memory B cells?. Immunol Lett, 2013; 152:114–120.
17.
SanzI, WeiC, LeeFE, AnolikJ: Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol, 2008; 20:67–82.
18.
JacobiAM, ReiterK, MackayM, et al.: Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: Delineation by expression of CD27, IgD, and CD95. Arthritis Rheum, 2008; 58:1762–1773.
19.
AdlowitzDG, BarnardJ, BiearJN, et al.: Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLoS One, 2015; 10:e0128269.
20.
CeruttiA, ColsM, PugaI: Marginal zone B cells: Virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol, 2013; 13:118–132.
21.
DiLilloDJ, MatsushitaT, TedderTF: B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. Ann N Y Acad Sci, 2010; 1183:38–57.
22.
ReynaudCA, DescatoireM, DoganI, HuetzF, WellerS, WeillJC: IgM memory B cells: A mouse/human paradox. Cell Mol Life Sci, 2012; 69:1625–1634.
23.
WeillJC, WellerS, ReynaudCA: Human marginal zone B cells. Annu Rev Immunol, 2009; 27:267–285.
24.
PillaiS, CariappaA: The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol, 2009; 9:767–777.
25.
AvrameasS, SelmiC: Natural autoantibodies in the physiology and pathophysiology of the immune system. J Autoimmun, 2013; 41:46–49.
26.
BaumgarthN: Innate-like B cells and their rules of engagement. Adv Exp Med Biol, 2013; 785:57–66.
27.
Good-JacobsonKL, TarlintonDM: Multiple routes to B-cell memory. Int Immunol, 2012; 24:403–408.
28.
TangyeSG, GoodKL: Human IgM+CD27+ B cells: Memory B cells or “memory” B cells?. J Immunol, 2007; 179:13–19.
29.
SeifertM, PrzekopowitzM, TaudienS, et al.: Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions. Proc Natl Acad Sci U S A, 2015; 112:E546–E555.
30.
PugaI, ColsM, BarraCM, et al.: B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol, 2012; 13:170–180.
31.
LevinsonP, KaulR, KimaniJ, et al.: Levels of innate immune factors in genital fluids: Association of alpha defensins and LL-37 with genital infections and increased HIV acquisition. AIDS, 2009; 23:309–317.
32.
HoJL, HeS, HuA, et al.: Neutrophils from human immunodeficiency virus (HIV)-seronegative donors induce HIV replication from HIV-infected patients' mononuclear cells and cell lines: An in vitro model of HIV transmission facilitated by Chlamydia trachomatis. J Exp Med, 1995; 181:1493–1505.
33.
ArnoldKB, BurgenerA, BirseK, et al.: Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol, 2016; 9:194–205.
34.
CorcioneA, FerlitoF, GattornoM, et al.: Phenotypic and functional characterization of switch memory B cells from patients with oligoarticular juvenile idiopathic arthritis. Arthritis Res Ther, 2009; 11:R150.
35.
LiuRX, WeiY, ZengQH, et al.: Chemokine (C-X-C motif) receptor 3-positive B cells link interleukin-17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma. Hepatology, 2015; 62:1779–1790.
36.
SchierlohP, LandoniV, BalboaL, et al.: Human pleural B-cells regulate IFN-gamma production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction. Clin Sci (Lond), 2014; 127:391–403.
37.
MizuochiT, ItoM, SaitoK, et al.: Possible recruitment of peripheral blood CXCR3+ CD27+ CD19+ B cells to the liver of chronic hepatitis C patients. J Interferon Cytokine Res, 2010; 30:243–252.
38.
HarrisDP, GoodrichS, GerthAJ, PengSL, LundFE: Regulation of IFN-gamma production by B effector 1 cells: Essential roles for T-bet and the IFN-gamma receptor. J Immunol, 2005; 174:6781–6790.
39.
LajoieJ, PoudrierJ, Massinga LoembeM, et al.: Chemokine expression patterns in the systemic and genital tract compartments are associated with HIV-1 infection in women from Benin. J Clin Immunol, 2010; 30:90–98.
40.
CastellsagueX, GiulianoAR, GoldstoneS, et al.: Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine, 2015; 33:6892–6901.
41.
HillmanRJ, GiulianoAR, PalefskyJM, et al.: Immunogenicity of the quadrivalent human papillomavirus (type 6/11/16/18) vaccine in males 16 to 26 years old. Clin Vaccine Immunol, 2012; 19:261–267.
42.
KamathGR, ShahDP, HwangLY: Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis. Vaccine, 2014; 32:2265–2274.
43.
BaralS, ShermanSG, MillsonP, BeyrerC: Vaccine immunogenicity in injecting drug users: A systematic review. Lancet Infect Dis, 2007; 7:667–674.
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