Responses to pandemic AS03-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals

ABSTRACT: BACKGROUND: Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. OBJECTIVE: Assess vaccine-related effects on CD4+ T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. METHODS: A single dose of ArepanrixTM split vaccine including 3.75 mug A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1--5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4+ T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. RESULTS: Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4+ T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4+ T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4+ T cell numbers, which was greater amongst responders. CONCLUSIONS: We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4+ T cell numbers, which was accentuated in responders. A single injection of the ArepanrixTM pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.     

Long-term immunogenicity after one and two doses of a monovalent MF59-adjuvanted A/H1N1 Influenza virus vaccine coadministered with the seasonal 2009-2010 nonadjuvanted Influenza virus vaccine in HIV-infected children, adolescents, and young adults in a randomized controlled trial

Few data are available on the safety and long-term immunogenicity of A/H1N1 pandemic influenza vaccines for HIV-infected pediatric patients. We performed a randomized controlled trial to evaluate the safety and long-term immunogenicity of 1 versus 2 doses of the 2009 monovalent pandemic influenza A/H1N1 MF59-adjuvanted vaccine (PV) coadministered with the seasonal 2009-2010 trivalent nonadjuvanted influenza vaccine (SV) to HIV-infected children, adolescents, and young adults. A total of 66 HIV-infected patients aged 9 to 26 years were randomized to receive one (group 1) or two (group 2) doses of PV coadministered with 1 dose of SV. The main outcome was the seroconversion rate for PV at 1 month. Secondary outcomes were the geometric mean titer ratios and the seroprotection rates at 1 month for all vaccines, seroconversion rates at 1 month for SV, and longitudinal changes of antibody titers (ABTs) at 1, 2, 6, and 12 months for all vaccines. Groups 1 and 2 had similar CD4 counts and HIV RNA levels during the study. The seroconversion rate for PV was 100% at 1 month in both groups. ABTs for PV were high during the first 6 months and declined below seroprotection levels thereafter. Longitudinal changes in ABTs were similar in groups 1 and 2 for both PV and SV. The side effects of vaccination were mild and mostly local. In HIV-infected children, adolescents, and young adults, the immune response triggered by a single dose of PV was similar to that obtained with a double dose and was associated with long-term antibody response.     

Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.     

Immunogenicity and effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy

In order to evaluate the immunogenicity and the effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy (HAART), 29 children infected with HIV-1 vertically (19 primed with a previous influenza vaccination and 10 who were not been immunized against influenza) were immunized with an intramuscular virosome-adjuvanted influenza vaccine. According to the European Agency for Evaluation of Medical Products (EMEA) criteria, the immunogenicity of the vaccine was adequate against all three influenza strains (A H1N1, A H3N2, and B) in the primed children, and against A H1N1 and A H3N2 in the unprimed children. After in vitro stimulation with vaccine antigens, the IFN-gamma levels in the peripheral blood mononuclear cells cultures increased significantly from a baseline level of 103.0 +/- 229.8 pg/ml to a 30-day level of 390.7 +/- 606.3 pg/ml (P < 0.05), with concentrations significantly higher (P < 0.05) in the primed children than in the unprimed children. No increase in plasma HIV-1 RNA or HIV-1 proviral DNA was observed in either subgroup, and the immunophenotype analyses demonstrated that the CD4+ cell counts and percentages, the CD4/CD8 ratio and activated lymphocytes remained stable in either group from baseline to 1 month after each vaccine dose. This study showed that the virosomal influenza vaccine does seem to be immunogenic in the majority of HIV-infected children receiving HAART and does not induce viral replication or T-cell activation. Given the possible influenza-related complications in children infected with HIV, these results support the use of this influenza vaccine in such patients.     

Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected individuals

The impact of pandemic (H1N1) 2009 influenza in HIV-infected individuals is unknown. Determining the prevalence of pandemic influenza in this at-risk group will guide vaccination programs. After the first pandemic wave, the seroprevalence rate of pandemic influenza in HIV-infected individuals in western Sydney, New South Wales, Australia, was 34.2%, similar to the rate observed in the general population. However, true seroprevalence is more accurately determined by seroconversion, defined as a 4-fold or greater rise between preexposure and postexposure antibody levels, which was 14.6% in the present study. Seroconversion rates were independent of CD4 T-lymphocyte count and HIV plasma load. Neither HIV infection, nor severe immunosuppression, was a significant risk factor for pandemic influenza during the first southern hemisphere pandemic wave.     

High Non‐Specific T Lymphocyte Response to the Adjuvanted H1N1 Vaccine in Comparison with the H1N1/H3N2/B‐Brisbane Vaccine without Adjuvant

Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non‐adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non‐specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1‐specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene‐based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non‐adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B‐Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1‐induced immunogenicity was good for both vaccines. Our results suggest a pronounced non‐specific T cell response after AS03‐adjuvanted 2009 H1N1 vaccination.     

Influenza and HIV: Lessons from the 2009 H1N1 Influenza Pandemic

Influenza is a common respiratory disease in adults, including those infected with HIV. In the spring of 2009, a pandemic influenza A (H1N1) virus (pH1N1) emerged. In this article, we review the existing literature regarding pH1N1 virus infection in HIV-infected adults, which suggests that susceptibility to pH1N1 virus infection and severity of influenza illness are likely not increased in HIV-infected adults without advanced immunosuppression or comorbid conditions. The risk of influenza-related complications, however, may be increased in those with advanced immunosuppression or high-risk comorbid conditions. Prevention and treatment of high-risk comorbid conditions and annual influenza vaccination should continue to be part of HIV clinical care to help prevent influenza illness and complications. Additional information about pH1N1 vaccine immunogenicity and efficacy in HIV-infected patients would be useful to guide strategies to prevent influenza virus infection in this population.     

Contemporary seasonal influenza A (H1N1) virus infection primes for a more robust response to split inactivated pandemic influenza A (H1N1) Virus vaccination in ferrets

Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8(+) cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.     

Optimizing the immunogenicity of pandemic H1N1 2009 influenza vaccine in adult organ transplant patients

Pandemic H1N1 influenza presented a significant threat to vulnerable immunocompromised hosts. Vaccination provided the best method of prevention, both for individuals and for herd immunity. Numerous studies have shown that the antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients is diminished compared with normal hosts. Techniques to improve response to influenza vaccination, including multiple doses, use of adjuvants, different delivery methods and doses have been investigated in transplant patients. The recent article in Transplant International by Felldin et al. evaluating the humoral immune response to two serial doses of pandemic H1N1 2009 influenza vaccine in adult organ transplant recipients is reviewed.     

儿童甲型H1N1流感和季节性流感患者的病毒载量及相关临床症状研究

目的 分析并比较儿童甲型H1N1流感和季节性流感患者咽拭子标本的病毒载量及相关临床症状.方法 应用荧光PCR方法对采集的咽拭子标本进行检测,并通过建立核酸标准品,绘制标准曲线,测定标本中的病毒载量,同时结合所收集的患者临床症状数据资料应用随机区组方差和卡方检验方法进行统计分析.结果 2009年9月至2010年9月期间收集的1,040份咽拭子标本中,共检出甲型H1N1流感病毒阳性标本120份,甲型H3N2流感病毒阳性标本61份,乙型流感病毒阳性标本99份;对收集的流感阳性标本病毒载量测定结果显示:不同型别,不同发病时间流感患者咽拭子标本的病毒载量差异无统计学意义(P＞0.05);甲型H1N1流感、季节性流感感染者的性别比例差异无统计学意义,甲型H1N1流感感染者出现咳嗽,流涕临床症状者明显高于与乙型流感感染者.结论 甲型H1N1流感患者咳嗽,流涕症状比季节性乙型流感患者多见,而甲型H1N1流感和季节性流感患者咽拭子标本的病毒载量无显著性差异.     

Humoral and cellular response to influenza vaccine in HIV-infected children with full viroimmunologic response to antiretroviral therapy

OBJECTIVE: It is unclear whether the ability to respond to vaccines is restored by antiretroviral therapy. We evaluated the influenza-specific immune responses elicited by a virosomal vaccine in HIV-infected children on long-term successful highly active antiretroviral therapy (HAART). METHODS: This was an observational, prospective, open-label study enrolling 24 HIV-infected, HAART-treated (85 months' mean exposure), vaccine-naive children (median age=11.9 years) and 14 age- and gender-matched healthy controls. Mean CD4 T-cell counts (>900 cells/microL) and percentages (>37%) were comparable. The HIV RNA level was <50 copies/mL in all patients. Children received a single dose of trivalent virosome-adjuvanted influenza vaccine. A/H3N2-, A/H1N1-, and B-antigen-specific antibody (Ab) titers and subclasses and vaccine-specific interferon-gamma (IFNgamma)- and interleukin (IL)-2-producing T lymphocytes were analyzed at baseline and 1 and 6 months after immunization. RESULTS: Seroconversion (>or=4-fold Ab titer raise in >40% of patients) and seroprotection (Ab titer>or=1:40 in >70% of patients) was achieved at 1 month in both groups; however, fewer HIV-infected children fulfilled these criteria. The A/H3N2- and A/H1N1-specific Ab geometric mean titers were lower in HIV-infected children compared with healthy controls at 1 and 6 months; interestingly, a boost in vaccine-specific IgG3 T helper 1 type Ab was seen in healthy controls alone. Finally, vaccine specific-IFNgamma- and IL-2-producing T lymphocytes were reduced at both time points in HIV-infected children compared with healthy controls. CONCLUSIONS: One injection of virosomal-adjuvanted influenza vaccine stimulates good immune responses, although the humoral and cellular immune responses are reduced in HIV-infected children compared to healthy children. This indicates that immunologic function impairments may persist upon HIV infection even if HIV-positive viremia is suppressed and immune recovery seems to be achieved.     

Reduced antibody responses to the pandemic (H1N1) 2009 vaccine after recent seasonal influenza vaccination

The vaccination program against the 2009 pandemic H1N1 influenza virus (2009 H1N1) provided a unique opportunity to determine if immune responses to the 2009 H1N1 vaccine were affected by a recent, prior vaccination against seasonal influenza virus. In the present study, we studied the immune responses to the 2009 H1N1 vaccine in subjects who either received the seasonal influenza virus vaccination within the prior 3 months or did not. Following 2009 H1N1 vaccination, subjects previously given a seasonal influenza virus vaccination exhibited significantly lower antibody responses, as determined by hemagglutination inhibition assay, than subjects who had not received the seasonal influenza virus vaccination. This result is compatible with the phenomenon of "original antigenic sin," by which previous influenza virus vaccination hampers induction of immunity against a new variant. Our finding should be taken into account for future vaccination programs against pandemic influenza virus outbreaks.     

Generation of human neutralizing monoclonal antibodies against the 2009 pandemic H1N1 virus from peripheral blood memory B lymphocytes

The 2009 H1N1 influenza pandemic demonstrated the significance of a global health threat to human beings. Although pandemic H1N1 vaccines have been rapidly developed, passive serotherapy may offer superior immediate protection against infections in children, the elderly and immune-compromised patients during an influenza pandemic. Here, we applied a novel strategy based on Epstein–Barr virus (EBV)-immortalized peripheral blood memory B cells to screen high viral neutralizing monoclonal antibodies (MAbs) from individuals vaccinated with the 2009 pandemic H1N1 vaccine PANFLU.1. Through a massive screen of 13 090 immortalized memory B-cell clones from three selected vaccinees, seven MAbs were identified with both high viral neutralizing capacities and hemagglutination inhibition (HAI) activities against the 2009 pandemic H1N1 viruses. These MAbs may have important clinical implications for passive serotherapy treatments of infected patients with severe respiratory syndrome, especially children, the elderly and immunodeficient individuals. Our successful strategy for generating high-affinity MAbs from EBV-immortalized peripheral blood memory B cells may also be applicable to other infectious or autoimmune diseases.     

Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice

In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD₅₀]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice.     

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults

Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75μg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.     

Immunoglobulin G subclass levels and antibody responses to the 2009 influenza A (H1N1) monovalent vaccine among human immunodeficiency virus (HIV)-infected and HIV-uninfected adults

Immunoglobulin (Ig)G levels are important for antibody vaccine responses and IgG subclass deficiencies have been associated with severe 2009 influenza A (H1N1) infections. Studies have demonstrated variations in immune responses to the H1N1 vaccine, but the aetiology of this is unknown. We determined the associations between pre‐vaccination overall and influenza‐specific IgG subclass levels and 2009 H1N1‐specific antibody responses post‐vaccination (robust versus poor at day 28) stratified by human immunodeficiency virus (HIV) status. Logistic regression models were utilized to evaluate whether pre‐vaccination IgG subclass levels were associated with the antibody response generated post‐vaccination. We evaluated 48 participants as part of a clinical study who were stratified by robust versus poor post‐vaccination immune responses. Participants had a median age of 35 years; 92% were male and 44% were Caucasian. HIV‐infected adults had a median CD4 count of 669 cells/mm³, and 79% were receiving highly active anti‐retroviral therapy. HIV‐infected participants were more likely to have IgG2 deficiency (<240 mg/dl) than HIV‐uninfected individuals (62% versus 4%, P < 0·001). No association of pre‐vaccination IgG subclass levels (total or influenza‐specific) and the antibody response generated by HIN1 vaccination in either group was found. In summary, pre‐vaccination IgG subclass levels did not correlate with the ability to develop robust antibody responses to the 2009 influenza A (H1N1) monovalent vaccine. IgG2 deficiencies were common among HIV‐infected individuals but did not correlate with poor influenza vaccine responses. Further investigations into the aetiology of disparate vaccine responses are needed.     

Genetic variability of isolates of pandemic influenza virus A H1N1 isolated in Russia in 2009

In 14 isolates of pandemic influenza virus A H1N1 extracted from patients with influenza in 2009, complete nucleotide sequences of genome segments encoding surface proteins hemagglutinin and neuraminidase were determined. Phylogenetic analysis of these sequences showed their genetic similarity with the corresponding genes of other isolates of pandemic influenza virus A (H1N1) 2009 extracted in other countries, and the degree of homology for each gene was over 99%. Neuraminidase mutations known in the literature that lead to the stability of the virus to oseltamivir and other drugs of neuraminidase inhibitors were not recorded in the studied isolates. In four isolates from autopsy material, G155E mutation was found in hemagglutinin of the isolate A/Salekhard/01/2009 (H1N1). This mutation leads to increased viral replication in developing chick embryos. The frequency and nature of the nucleotide substitutions in the hemagglutinin and neuraminidase genes are determined.     

T淋巴细胞在甲型H1N1流感病毒感染中的变化及意义

目的 研究甲型H1N1流行性感冒(流感)患者外周血T淋巴细胞及其激活亚群的变化.方法 用流式细胞仪检测144例甲型HlNl流感患者和41例健康体检者淋巴细胞亚群,对其中83例患者进一步分析治疗前后T淋巴细胞及其激活亚群(HLA-DR+CD3+、HLA-DR+CD4+和HLA-DR+CD8+细胞).结果 ①与对照组相比,H1N1并发肺炎组和H1N1组淋巴细胞数明显低于对照组,H1N1并发肺炎组淋巴细胞数明显低于H1N1组;H1N1并发肺炎组T淋巴细胞百分比明显低于对照组(P<0.05).②治疗前后CD3、CD8细胞百分比和绝对数均差异有统计学意义,治疗前显著降低,CD4细胞数治疗前显著降低.③治疗前后T淋巴细胞激活亚群(HLA-DR+CD3+、HLA-DR+CD4+和HLA-DR+CD8+细胞)百分比差异有统计学意义,治疗前显著降低.结论 测定甲型H1N1流感患者外周血T淋巴细胞及其激活亚群的变化有助于评价甲型H1N1流感患者感染早期的细胞免疫状况,可以作为甲型H1N1流感早期诊断的辅助指标.     

T淋巴细胞在甲型H1N1流感病毒感染中的变化及意义

目的 研究甲型H1N1流行性感冒(流感)患者外周血T淋巴细胞及其激活亚群的变化.方法 用流式细胞仪检测144例甲型HlNl流感患者和41例健康体检者淋巴细胞亚群,对其中83例患者进一步分析治疗前后T淋巴细胞及其激活亚群(HLA-DR+CD3+、HLA-DR+CD4+和HLA-DR+CD8+细胞).结果 ①与对照组相比,H1N1并发肺炎组和H1N1组淋巴细胞数明显低于对照组,H1N1并发肺炎组淋巴细胞数明显低于H1N1组;H1N1并发肺炎组T淋巴细胞百分比明显低于对照组(P<0.05).②治疗前后CD3、CD8细胞百分比和绝对数均差异有统计学意义,治疗前显著降低,CD4细胞数治疗前显著降低.③治疗前后T淋巴细胞激活亚群(HLA-DR+CD3+、HLA-DR+CD4+和HLA-DR+CD8+细胞)百分比差异有统计学意义,治疗前显著降低.结论 测定甲型H1N1流感患者外周血T淋巴细胞及其激活亚群的变化有助于评价甲型H1N1流感患者感染早期的细胞免疫状况,可以作为甲型H1N1流感早期诊断的辅助指标.