BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ² test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.
Female ; Follow-Up Studies ; HIV Infections/immunology* ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/administration & dosage* ; Humans ; Immunization Schedule ; Male

A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
AIDS Vaccines ; chemistry ; immunology ; Antibodies, Neutralizing ; immunology ; HIV Antibodies ; immunology ; HIV Envelope Protein gp41 ; immunology ; HIV-1 ; chemistry ; immunology ; Humans

Objective: To study the diagnostic and epidemiological features of the first two HIV-2 indigenous cases in Hunan province. Methods: Blood samples from two individuals with "HIV antibody indeterminate" and HIV-2 specific band showed by HIV-1/2 western blotting method, were repeatedly collected and detected under HIV 1+2 strip immunoassay and PCR, in Changsha city, Hunan province, through March to November, 2017. An epidemiological survey was carried out at the same time. Results: Our findings showed that the two cases were sex partners, without histories of sexual contact with foreigners and the source of infection was unknown. Results from the HIV 1+2 antibody confirmation test showed that they were "HIV-2 antibody positive" . Through amplifying and sequencing the gag area of HIV-2 and BLAST, the similarity of HIV-2 strains presented as 98%. The results also showed that there were HIV-2 specific fragments in the two cases. Conclusion: HIV-2 indigenous cases had never been reported in China. These cases had brought new challenge on prevention, diagnosis and treatment of HIV/AIDS in China.
Adult ; Blotting, Western/methods* ; China ; HIV Antibodies/isolation & purification* ; HIV Infections/ethnology* ; HIV-2/immunology* ; Humans ; Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires

Objective: To identify the influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests, to provide scientific evidence for the differential diagnosis of HIV infection and control strategy. Methods: A case control study was conducted. The samples of HIV antibody indeterminate in confirmed Western blot (WB) tests, but were negative in HIV nucleic acid tests, were collected as HIV antibody indeterminate group from WB results of HIV confirmatory laboratories of Fujian province in 2015-2016. The general population matched group with HIV antibody screening negative samples and WB negative matched group with WB negative samples were selected as the two compared groups by matching gender and age from HIV antibody screening in Fujian province in the same period. Blood concentrations of hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-treponema pallidum (TP) antibody, antinuclear antibody (ANA), anti-human T-cell leukemia virus (HTLV) antibody, and alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay (ELISA). χ(2) test and multivariate non-conditional logistic regression analysis were performed to identify the influencing factors that leading to nonspecific responses, to indeterminate HIV antibody tests. Results: A total of 13 WB band patterns were observed in 110 HIV antibody indeterminate samples, in which a single p24 band (58.18%, 64/110), a single gp160 band (17.27%, 19/110) and a single p17 band (7.27%, 8/110) were the three most common patterns. The positive rate of anti-TP antibody was significantly higher in HIV antibody indeterminate samples than general population control group and WB negative control group (10.91%, 12/110 vs. 1.77%, 4/226 and 3.64%, 4/110), compared with two control groups (χ(2)=13.627 and 4.314, P<0.05). The positive rate of AFP was significantly higher in HIV antibody indeterminate samples than general population control group (18.18%, 20/110 vs. 0.44%, 1/226, χ(2)=39.736, P<0.05), the different was not significant compared with WB negative control group (18.18%, 20/110 vs. 23.64%, 26/110, χ(2)=0.990, P>0.05) While no significant differences were found between HIV antibody indeterminate group and two control groups in terms of the positive rates of ANA, HBsAg, anti-HCV antibody or anti-HTLV antibody. Conclusions: The influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests appeared complicate, and the anti-TP antibody positivity might be an influencing factor responsible for nonspecific responses to indeterminate HIV antibody tests.
Adult ; Blotting, Western/methods* ; Case-Control Studies ; China/epidemiology* ; Enzyme-Linked Immunosorbent Assay/methods* ; HIV Antibodies/isolation & purification* ; HIV Infections/epidemiology* ; HIV-1/immunology* ; Humans ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity

Therapeutic HIV vaccine was considered as a hopeful curative method for AIDS patients. However, there is still no suitable HIV animal model for vaccine study since the difference in the immune system between human and animals. To evaluate the therapeutic effect of combined immunization strategy with multiple vector vaccines in macaque models. Plasmid DNA, recombinant Ad5 and MVA vaccines which expressing SIV gag and env genes were constructed. Sequential and repeated immune strategy were applied to immunize mice with these three vaccines. Cellular immune responses in mice immunized with these three vaccines were measured by ELISPOT test in vitro and CTL assay in vivo. The results were analyzed and compared with different antigen combination, order of vaccines and intervals to choose a suitable immunization strategy for macaque immunization in future. It indicated that strong SIV-Gag/Env-specific cellular immune responses were induced by these three vector vaccines. It laid a foundation for evaluating the therapeutic effect of combined immunization strategy with multiple vector vaccines in SIV infected macaque models.
AIDS Vaccines ; administration & dosage ; genetics ; immunology ; Adenoviridae ; genetics ; metabolism ; Animals ; Antibodies, Viral ; immunology ; Female ; Gene Products, env ; administration & dosage ; genetics ; immunology ; Gene Products, gag ; administration & dosage ; genetics ; immunology ; Genetic Vectors ; genetics ; metabolism ; HIV Infections ; immunology ; prevention & control ; virology ; Humans ; Immunization ; Mice ; Mice, Inbred BALB C ; Simian Immunodeficiency Virus ; genetics ; immunology ; Vaccines, DNA ; administration & dosage ; genetics ; immunology

A safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is expected to have a considerable impact on elimination of acquired immune deficiency syndrome. Despite decades of effort, an effective vaccine against HIV-1 remains elusive. In recent years, the Thai HIV Vaccine Efficacy Trial (known as RV144) showed a reduction in HIV-1 acquisition by 31%, but this agent could not delay disease progression in vaccinated individuals. Clinical analyses of experimental data and experiments in vitro have revealed two main types of immunogen design: induction of broad-spectrum neutralizing antibody (bNAb) and cytotoxic T lymphocyte (CTL) responses. bNAb can prevent or reduce acquisition of infection, and its main immunogens are virus-like particles, natural envelope trimers and stable bNAb epitopes. An effective CTL response can slow-down viral infection, and its main immunogens are "mosaic" vaccines, "conserved immunogens", and the "fitness landscape" of HIV-1 proteins. This review summarizes the strategies as well as progress in the design and testing of HIV-1 immunogens to elicit bNAb and CTL responses.
AIDS Vaccines ; genetics ; immunology ; Animals ; Drug Design ; HIV Antibodies ; immunology ; HIV Infections ; immunology ; prevention & control ; virology ; HIV-1 ; genetics ; immunology ; Humans

BACKGROUNDThe prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART)-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults.

METHODSWe performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression.

RESULTSA total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P = 0.006 and P = 0.044, respectively). The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm 3 (3.3%) and >350 cells/mm 3 (2.8%) compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1%) (P = 0.002 and P = 0.005, respectively). The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001). We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7%) versus men who have sex with men (3.9%) (P = 0.002) and versus heterosexual transmission (3.9%) (P = 0.001). In binary logistic regression analyses, age ≥ 50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018), 2.091 (95% CI: 1.078, 4.055, P = 0.029) and 2.259 (95% CI: 1.028, 4.962, P = 0.042), respectively.

CONCLUSIONSThrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years), HCV-Ab positivity and lower CD4+ cell count are associated with an increased risk of thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.

Adult ; CD4 Lymphocyte Count ; Cross-Sectional Studies ; Female ; HIV Infections ; blood ; epidemiology ; immunology ; Hepatitis C Antibodies ; blood ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thrombocytopenia ; blood ; epidemiology ; etiology

To enhance the immunogenicity of DNA and adenoviral vector vaccines expressing HIV-1 subtype B gp160, human interleukin 15 (hIL15) DNA adjuvant (pVR-hIL15) was constructed. BALB/c mice received DNA prime/protein boost immunization with pVR-HIVgp160/Ad5-HIVgp160 alone or combined with pVR-hIL15. Cellular and humoral immune responses were evaluated by IFN-gamma enzyme-linked immunosorbent spot assay and enzyme-linked immunosorbent assay, respectively. Compared with those immunized with vaccines alone, the mice immunized with vaccines combined with pVR-hIL15 had significantly increased specific cellular response and antibody titer (P < 0.05). It suggests that the IL15 DNA adjuvant can enhance the immune responses induced by prime-boost regimen using DNA and adenoviral vector encoding HIV-1 subtype B gp160.
Adenoviridae ; genetics ; Adjuvants, Immunologic ; Animals ; Antibodies, Viral ; immunology ; Antibody Specificity ; Female ; Genetic Vectors ; genetics ; HIV Envelope Protein gp120 ; immunology ; HIV Envelope Protein gp160 ; genetics ; immunology ; HIV Envelope Protein gp41 ; immunology ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Interleukin-15 ; genetics ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA ; genetics ; immunology

OBJECTIVETo investigate the potential of hepatitis C virus (HCV) antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus (HIV) co-infection.

METHODSA total of 340 individuals who tested positive for serum anti-HCV antibodies and/or serum anti-HW antibodies were enrolled for study in 2009 from a single village in central China. Markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and infection (anti-HCV antibodies, CD4⁺ T cell counts, HCV genotype, and HCV viral load) were measured at baseline and follow-up (in July 2012). At follow-up,the subjects were grouped according to ongoing HCV mono-infection (n=129), ongoing HCV/HIV co-infection (n=98), spontaneously resolved (SR)-HCV in mono-infection (n=65), and SR-HCV in HCV/HIV co-infection (n=48) for statistical analysis.

RESULTSAlmost all of the subjects in the ongoing HCV mono-infection group showed high levels of HCV antibodies (S/CO more than or equal to 10), but the majority of the subjects in the SR-HCV in mono-infection group and in the ongoing HCV/HIV co-infection group. The SR-HCV mono-infection group showed a remarkable decrease in HCV antibodies from 2009 (HIV:7.75 ± 3.8; HIV+:7.61 ± 3.47) to 2012 (HIV:5.51 ± 3.67; HIW:4.93 ± 3.35) (HIV:t =10.67, P less than 0.01; HIV+:t =9.52, P less than 0.01). The ongoing HCV/HIV co-infection group showed a positive correlation between HCV antibodies S/CO ratio and CD4⁺ T cell count (r=028, P=0.008). In the ongoing HCV mono-infection group,the levels of HCV antibodies were significantly higher in individuals infected with HCV-1b than in those with HCV-2a (14.74 ± 1.68 vs.14.08 ± 1.44, t=2.20, P=0.03). In the ongoing HCV/HIV co-infection group, the numbers of subjects with elevated (more than 40 U/L) liver function markers were significantly different according to the HCV genotype infection:HCV-1b:ALT, 25/42 vs.16/56 (x²=9.45, P=0.002); HCV2a:AST, 28/42 vs.18/56 (x²=11.49, P=0.001). The HCV RNA positive rate was significantly higher in subjects with high HCV antibody cutoff values (S/CO more than or equal to 10) than in those with low HCV antibody (S/CO less than 10) (HIV:128/151 vs.1/43, x²=102.11, P less than 0.01; HIV+:88/98 vs.10/48, x²=69.44, P less than 0.01), regardless of HIV co-infection. Significantly more subjects in the ongoing HCV mono-infection group had elevated (more than 40 U/L) ALT or AST than the subjects in the SR-HCV mono-infection group with high levels of HCV antibody (S/CO more than or equal to 10) (ALT:57/128 vs.2/23, x²=10.52, P=0.001; AST:57/128 vs.0/23, x²=16.45, P less than 0.01).

CONCLUSIONSerum HCV antibody levels, in combination with other clinical information such as liver function and HIV infection status, may aid in the preliminarily evaluation of an individual's HCV infection status and likelihood for spontaneous resolution. Low levels of HCV antibody (S/CO less than 10) may indicate a better chance of SR-HCV, after ruling out the possibility of suffering from immunosuppressive diseases such as HIV infection.

Adult ; CD4 Lymphocyte Count ; China ; epidemiology ; Coinfection ; immunology ; virology ; Female ; Genotype ; HIV Infections ; immunology ; Hepacivirus ; genetics ; Hepatitis C ; diagnosis ; immunology ; virology ; Hepatitis C Antibodies ; blood ; Humans ; Male ; Middle Aged ; RNA, Viral ; blood ; Serologic Tests ; Viral Load