Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effect of a fourth dose of vaccine

ObjectiveAlthough HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5 year period after either 3 or 4 doses of QHPV.Design/methodsHIV-infected children, ages 7-to-11 years, received 3 doses of QHPV (n = 96) or placebo (n = 30). At 72 weeks QHPV recipients received a fourth dose (n = 84), while placebo recipients began the 3-dose QHPV schedule (n = 27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5 years after the last dose of QHPV in each treatment arm.ResultsAt 4-to-5 years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86–93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1 month after completing vaccination.ConclusionsChildren with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels.Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556.     

A safe and sensitive enterovirus A71 infection model based on human SCARB2 knock-in mice

Enterovirus A71 infection has become a severe threat for global public health. Vaccines for controlling and preventing Enterovirus A71 epidemics are highly demanded, however, vaccine evaluation has been hindered by the lack of suitable Enterovirus A71 infection animal models. Here we established an hSCARB2 knockin mouse model for real-time monitoring of enterovirus A71 infection in vivo. This model was sensitive to the infection of both replication-competent virus rEV71(FY)-EGFP and single round pseudotype virus pEV71(FY)-Luc. The intensity of bioluminescence correlated well with viral loads in infected tissues (R = 0.86, P < 0.01). Pathological changes recapitulated human infectious and clinical features of enterovirus A71, including both general characteristics of “hand foot and mouth” and the severe symptoms in the CNS. A formalin-inactivated enterovirus A71 vaccine can elicit antibodies in R26-hSCARB2 mice, which play effective roles in protecting knockin mice against enterovirus A71 infection as indicated by bioluminescence. Therefore, this work provides a safe, sensitive and visualizing model for exploring mechanisms of enterovirus A71 infection and examining human enterovirus A71 vaccines and antiviral therapies.     

Cost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States

IntroductionIn the United States, routine human papillomavirus (HPV) vaccination is recommended for females and males at age 11 or 12 years; the series can be started at age 9 years. Vaccination is also recommended for females through age 26 years and males through age 21 years. The objective of this study was to assess the health impact and cost-effectiveness of harmonizing female and male vaccination recommendations by increasing the upper recommended catch-up age of HPV vaccination for males from age 21 to age 26 years.MethodsWe updated a published model of the health impact and cost-effectiveness of 9-valent human papillomavirus vaccine (9vHPV). We examined the cost-effectiveness of (1) 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years, and (2) an expanded program including males through age 26 years.ResultsCompared to no vaccination, providing 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years cost an estimated $16,600 (in 2016 U.S. dollars) per quality-adjusted life year (QALY) gained. The estimated cost per QALY gained by expanding male vaccination through age 26 years was $228,800 and ranged from $137,900 to $367,300 in multi-way sensitivity analyses.ConclusionsThe cost-effectiveness ratios we estimated are not so favorable as to make a strong economic case for recommending expanding male vaccination, yet are not so unfavorable as to preclude consideration of expanding male vaccination. The wide range of plausible results we obtained may underestimate the true degree of uncertainty, due to model limitations. For example, the cost per QALY might be less than our lower bound estimate of $137,900 had our model allowed for vaccine protection against re-infection. Models that specifically incorporate men who have sex with men (MSM) are needed to provide a more comprehensive assessment of male HPV vaccination strategies.     

Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients

BackgroundThe analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients.MethodsWe performed a subanalysis of a clinical trial that compared the safety and efficacy of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-α) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [≥4-fold increase in hemagglutination inhibition antibody titers] to ≥1 influenza vaccine antigen).ResultsMean baseline IL-6 levels were higher (1.20 versus 0.65 pg/mL; P-value = 0.021) and IL-2 levels were lower (0.01 versus 0.50 pg/mL; P-value = 0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02–1.10; P-value = 0.002). Vaccination induced an increase in TNF-α (P-value <0.0001) and a decrease in IL-5 levels (P-value = 0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-α levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72 pg/mL; P-value = 0.009).ConclusionsBaseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4⁺ T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients.     

江苏省2011-2013年新报告HIV感染者/艾滋病患者新发感染状况分析

目的：了解江苏省新报告HIV感染者/艾滋病患者（HIV/AIDS）新发感染状况。方法收集2011-2013年江苏省每年新报告的HIV/AIDS及其一般人口学资料、感染途径、样本来源等相关信息,并收集血清或血浆样本,进行BED检测,计算新发感染比例,研究新发感染的影响因素。结果同性传播的HIV/AIDS中新发感染比例最高（29.19%）,其次是注射毒品（21.75%）,异性传播最低（17.40%）,不同感染途径间差异有统计学意义（P＜0.05）。新报告的HIV/AIDS中,与女性相比,男性更可能是新发感染（OR＝1.569,95%CI：1.168～2.107）;与＞35岁的相比,≤35岁的更可能是新发感染（OR＝1.556,95%CI：1.289～1.879）;与未婚相比,已婚有配偶的更可能是长期感染（OR＝0.789,95%CI：0.649～0.960）;与其他就诊者检测相比,通过检测咨询（OR＝2.278,95%CI：1.853～2.801）、专题调查（OR＝2.409,95%CI：1.860～3.120）及无偿献血人员检测（OR＝2.911,95%CI：2.118～4.001）更容易发现HIV新发感染者（P＜0.05）。结论江苏省新报告HIV/AIDS中MSM的新发感染比例最高;应加强主动监测,减少二代传播。     

Associations between intimate partner violence,violence-related policies,and HIV diagnosis rate among women in the United States

PurposeTo assess the association between state-level intimate partner violence (IPV) prevalence and HIV diagnosis rates among women in the United States and investigate the modifying effect of state IPV health care policies.MethodsData on HIV diagnosis rates were collected from HIV surveillance data from 2010 to 2015, and IPV prevalence data were collected from the National Intimate Partner and Sexual Violence Survey from 2010 to 2012. States were coded for IPV health care policies on training, screening, reporting, and insurance discrimination.ResultsStates with higher IPV prevalence was associated with higher HIV diagnoses among women (B = 0.02; 95% confidence interval [CI] = 0.003, 0.04; P = .02). State policies were a significant effect modifier (B = −0.05; 95% CI = −0.07, −0.02; P < .001). Simple slopes revealed that the association between IPV and HIV diagnosis rates was stronger in states with low IPV protective health care policies (B = 0.09; CI = 0.06, 0.13; P < .001) and moderate IPV protective policies (B = 0.05; 95% CI = 0.02, 0.07, P < .001), but not in states with high IPV protective policies (B = −0.009; 95% CI = −0.04, 0.02; P = .59).ConclusionsHIV prevention programs should target IPV and link to community resources. IPV-related policies in the health care system may protect the sexual health of women experiencing IPV.     

Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells

Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241–259, 294–315, 317–327, 346–361, 377–388 and 421–437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection. Nevertheless, the immunogenicity of these epitopes has never been assessed. Here, we displayed these epitopes on highly immunogenic bacteriophage virus-like particles (VLPs; MS2, PP7 and Qβ) platforms and assessed their immunogenicity in mice. Mice immunized with a mixture of VLPs displaying ZIKV envelope B-cell epitopes elicited anti-ZIKV antibodies. Although, immunized mice were not protected against a high challenge dose of ZIKV, sera – albeit at low titers – from immunized mice neutralized (in vitro) a low dose of ZIKV. Taken together, these results show that these epitopes are B-cell epitopes and they are immunogenic when displayed on a Qβ VLP platform. Furthermore, the results also show that immunization with VLPs displaying a single B-cell epitope minimally reduces ZIKV infection whereas immunization with a mixture of VLPs displaying a combination of the B-cell epitopes neutralizes ZIKV infection. Thus, immunization with a mixture of VLPs displaying multiple ZIKV B-cell epitopes is a good strategy to enhance ZIKV neutralization.     

A combined carrier-adjuvant system of peptide nanofibers and toll-like receptor agonists potentiates robust CD8+ T cell responses

Improving CD8+ T cell responses activated by subunit vaccination is crucial for improving vaccine efficacy and safety. Here we report a carrier-adjuvant system composed of self-assembling peptide nanofibers presenting an immunodominant antigen from herpes simplex virus (HSV) and toll-like receptor (TLR) agonists that induces robust effector and memory CD8+ T cell responses in mice. The effector function of vaccine-induced CD8+ T cells was influenced by the type of TLR agonist. The use of CpG (TLR9 agonist) resulted in significantly greater specific in vivo cytotoxicity and trended towards more cells producing both IFN-γ and TNF-α compared to gardiquimod (TLR7 agonist). Prime-boost immunization with peptide nanofibers combined with either adjuvant resulted in development of HSV-specific CD8+ memory T cells further demonstrating the capability of the carrier-adjuvant system to induce strong HSV-specific CD8+ T cell responses. Inclusion of peptide epitope-nanofibers in protein-based subunit vaccines should increase the functional spectrum of the vaccine-elicited immune response and protection.     

甘肃省2004-2018年丙型肝炎流行特征

  目的  分析甘肃省丙型病毒性肝炎流行特征及其变化趋势,为制定防制措施提供科学依据。  方法  收集2004-2018年甘肃省丙型肝炎报告病例资料,采用Excel 2010、SPSS 19.0及ArcGIS 10.5软件进行资料整理与统计分析。  结果  2004-2018年甘肃省累计报告丙型肝炎病例数为102 802例,其中死亡42例,报告发病率从2004年的12.39/10万上升到2018年的33.92/10万（χ2=9 849.90,P < 0.001）。报告发病率随着年龄的增长呈上升趋势（χ2=26 784.53,P < 0.001）,≥ 80岁年龄组报告发病率最高（94.09/10万）,≥ 50岁年龄组报告发病率均超过50.00/10万。报告病例中农民所占比例逐年上升,2018年农民所占的构成比达67.31%。14个市（自治州）报告发病率均呈增长趋势,累计报告发病率排在前三位的市（自治州）是武威市（1 098.42/10万）,张掖市（1 077.69/10万）和兰州市（692.55/10万）。  结论  甘肃省丙肝报告疫情仍呈上升趋势,应加强重点人群和地区疫情监测,加强健康教育,提高公众对丙肝的认识。