Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

Background

The timing of host cytokine responses to influenza vaccination is poorly understood.

Objectives

We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV‐related side effects.

Patients/Methods

Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14.

Results

Serum cytokine responses to TIV were evident as early as 3 hours post‐immunization. Compared to baseline, IFN‐γ and IP‐10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post‐vaccination. Although IL‐8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL‐8 was significantly lower compared to baseline. Interestingly, IL‐8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL‐6, IL‐2, IL‐8, IP‐10, MCP‐1, TNF‐α, TARC, and MCP‐4.

Conclusions

Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine‐induced reductions in IL‐8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.     

A pilot study of the immune response to whole inactivated avian influenza H7N1 virus vaccine in mice

Background Highly pathogenic avian influenza (HPAI) outbreaks in domestic poultry bring humans into close contact with new influenza subtypes and represent a threat to human health. In 1999, an HPAI outbreak of H7N1 virus occurred in domestic poultry in Italy, and a wild‐type virus isolate from this outbreak was chosen as a pandemic vaccine candidate. Objectives We conducted a pilot study to investigate the kinetics of the humoral immune response induced after immunisation with an egg grown whole inactivated H7N1 virus vaccine in BALB/c mice. Methods Mice were vaccinated with one or two doses of H7N1 vaccine (15 μg total protein) to investigate the influenza specific antibody secreting cell (IS‐ASC) and serum antibody responses. Results After the first dose of vaccine, only IgM IS‐ASC were detected in the spleen and bone marrow, whereas IgG, IgA and IgM IS‐ASC were found after the second dose. Low antibody titres were detected after the first immunisation, whilst the second dose of vaccine significantly boosted the HI (range 128–512), neutralising and IgG antibody titres. The IgG subclass response was dominated by IgG2a indicating a dominant Th1 response after the first vaccination, whereas a more mixed Th1/Th2 profile was observed after the second dose. Conclusions This pilot study shows the value of using a number of immunological methods to evaluate the quality of the immune response to potential pandemic candidate vaccines.     

Impaired IgM antibody responses to an influenza virus vaccine in adults with sickle cell anemia

Type-specific IgM and IgG antibody responses to a polyvalent influenza vaccine were evaluated in 16 adults with sickle cell anemia, with the use of an enzyme-linked immunosorbent assay. When compared to healthy controls, 8 out of the 16 patients had decreased or undetectable postvaccination anti-influenza IgM antibody levels. These patients were found to have significantly lower serum IgM levels and nondetectable splenic tissue (by 99Tc scans), as compared to those with normal IgM responses. Impaired IgM antibody primary immune responses may play a role in the pathogenesis of infectious complications seen in adult patients with sickle cell anemia.     

The mucosal and systemic immune responses elicited by a chitosan-adjuvanted intranasal influenza H5N1 vaccine

Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose‐sparing strategies and an efficient mass‐vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose‐sparing potential of a chitosan‐adjuvanted intranasal H5N1 (RG‐14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)‐adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non‐adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG‐14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan‐adjuvanted SU vaccine induced an immune response superior to that of the non‐adjuvanted SU vaccine. Compared with the non‐adjuvanted SU group, the chitosan‐adjuvanted SU vaccine elicited higher numbers of influenza‐specific antibody‐secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T‐helper 1/T‐helper 2 cytokine response in the chitosan‐adjuvanted SU groups, and these groups had an increased percentage of virus‐specific CD4⁺ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non‐adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan‐adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T‐helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4⁺ Th1 cells simultaneously secreting three different cytokines (INFγ⁺, IL2⁺ and INFα⁺). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross‐clade serum reactivity, improved B‐ and T‐cell responses and dose‐sparing potential of chitosan show that a chitosan‐adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.     

Live attenuated influenza virus vaccine reduces virus shedding of newborn piglets in the presence of maternal antibody

Background

Influenza A virus in swine (IAV‐S) causes an acute respiratory disease of swine which results in great economic losses in pig production. Major control strategies include the use of killed vaccines (KV) in breeding females to confer passive immunity to their offspring. A bivalent H1N1 and H3N2 NS1‐truncated live attenuated IAV‐S vaccine have recently become available, which showed promising results in young pigs.

Objective

The aim of this study was to investigate the effect of an intranasal vaccination of newborn pigs with or without maternally derived antibodies (MDA) on virus shedding (via nasal swabs tested by virus isolation).

Methods

The study was performed as intratracheal challenge experiments with either a heterologous H1N2 or H3N2 viruses.

Results and conclusion

The results of this study showed a significant decrease in the incidence and duration of shedding viable virus for vaccinated newborn piglets with or without MDA, providing strong evidence that intranasal vaccination is overcoming passively acquired maternal immunity. This study indicates that intranasal vaccination with a truncated NS1 live attenuated IAV‐S vaccine of newborn piglets with maternal antibodies can be a valuable tool for reducing the prevalence of heterologous H1N2 and H3N2 IAV‐S in pig herds.     

Development of a new candidate H5N1 avian influenza virus for pre‐pandemic vaccine production

Background Highly pathogenic H5N1 avian influenza viruses currently circulating in birds have caused hundreds of human infections, and pose a significant pandemic threat. Vaccines are a major component of the public health preparedness for this likely event. The rapid evolution of H5N1 viruses has resulted in the emergence of multiple clades with distinct antigenic characteristics that require clade‐specific vaccines. A variant H5N1 virus termed clade 2.3.4 emerged in 2005 and has caused multiple fatal infections. Vaccine candidates that match the antigenic properties of variant viruses are necessary because inactivated influenza vaccines elicit strain‐specific protection. Objective To address the need for a suitable seed for manufacturing a clade 2.3.4 vaccine, we developed a new H5N1 pre‐pandemic candidate vaccine by reverse genetics and evaluated its safety and replication in vitro and in vivo. Methods A reassortant virus termed, Anhui/PR8, was produced by reverse genetics in compliance with WHO pandemic vaccine development guidelines and contains six genes from A/Puerto Rico/8/34 as well as the neuraminidase and hemagglutinin (HA) genomic segments from the A/Anhui/01/2005 virus. The multi‐basic cleavage site of HA was removed to reduce virulence. Results The reassortant Anhui/PR8 grows well in eggs and is avirulent to chicken and ferrets but retains the antigenicity of the parental A/Anhui/01/2005 virus. Conclusion These results indicate that the Anhui/PR8 reassortant lost a major virulent determinant and it is suitable for its use in vaccine manufacturing and as a reference vaccine virus against the H5N1 clade 2.3.4 viruses circulating in eastern China, Vietnam, Thailand, and Laos.     

Safety and immunogenicity of an inactivated thimerosal‐free influenza vaccine in infants and children

Objective Few prospective studies of inactivated split virion influenza vaccine have been conducted in infants and children. Our objective was to evaluate the safety, reactogenicity and immunogenicity of a thimerosal‐free inactivated influenza vaccine (Fluvax^®; CSL Limited, Parkville, Australia) in children aged 6 months to <9 years. Methods A prospective, open‐label, phase III clinical trial was conducted in 298 healthy children previously unvaccinated with influenza, commencing in the Southern Hemisphere 2005 autumn. Participants were divided into two groups (Group A: ≥6 months to <3 years; Group B: ≥3 years to <9 years), and received two doses of the 2005 vaccine, and one dose of the 2006 vaccine one year later (Group A: 0·25 ml per dose; Group B: 0·5 ml per dose). Vaccine safety and reactogenicity was evaluated for 30 days after each dose. Immunogenicity was assessed using hemagglutination inhibition and single radial hemolysis assays. Results There were no withdrawals due to adverse events (AEs). The majority of solicited local and systemic AEs were of mild severity. A maximum intensity of severe was reported for injection site pain and fever by only 3·0% and 3·4% of participants, respectively. The vaccine was immunogenic for all antigens, with ≥95% of both younger and older children achieving seroprotection after dose 2. Conclusions This thimerosal‐free inactivated influenza vaccine had a favorable safety profile and was immunogenic in children aged ≥6 months and <9 years. Primary and booster vaccination produced consistently immunogenic responses including in children under 3 years of age receiving 0·25 ml doses of vaccine.     

Influenza: the virus and prophylaxis with inactivated influenza vaccine in ��at risk�� groups, including COPD patients

Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other “at risk” groups to reduce morbidity, save lives, and reduce health care costs.     

Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency

AIM： To investigate a novel DNA vaccination based upon expression of the HBV e antigen fused to a heat shock protein （HSP） as a strategy to enhance DNA vaccine potency.
METHODS： A pCMV-HBeAg-HSP DNA vaccine and a control DNA vaccine were generated. Mice were immunized with these different construct. Immune responses were measured 2 wk after a second immunization by a T cell response assay, CTL cytotoxicity assay, and an antibody assay in C57BL/6 and BALB/c mice. CT26-HBeAg tumor cell challenge test in vivo was Performed in BALB/c mice to monitor anti-tumor immune responses.
RESULTS： In the mice immunized with pCMV-HBe-HSP DNA, superior CTL activity to target HBV-positive target cells was observed in comparison with mice immunized with pCMV-HBeAg （44% ± 5% vs 30% ± 6% in E： T 〉 50：1, P 〈 0,05）, ELISPOT assays showed a stronger T-cell response from mice immunized with pCMV-HBe- HSP than that from pCMV-HBeAg immunized animals when stimulated either with MHC class I or class Ⅱ epitopes derived from HBeAg （74% ± 9% vs 31% ± 6%, P 〈 0.01）. ELISA assays revealed an enhanced HBeAg antibody response from mice immunized with pCMV- HBe-HSP than from those immunized with pCMV-HBeAg. The lowest tumor incidence and the slowest tumor growth were observed in mice immunized with pCMV- HBe-HSP when challenged with CT26-HBeAg.
CONCLUSION： The results of this study demonstrate a broad enhancement of antigen-specific CD4^＋ helper,CD8^＋ cytotoxic T-cell, and B-cell responses by a novel DNA vaccination strategy. They also proved a stronger antigen-specific immune memory, which may be superior to currently described HBV DNA vaccination strategies for the treatment of chronic HBV infection.     

Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

BACKGROUND/AIMS: Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS: In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS: A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-gamma production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS: Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.     

甲型H1N1流感患者Th1和Th2型细胞因子的检测及其意义

目的探讨甲型H1N1流感患者外周血Th1和Th2细胞因子的表达水平,为临床诊断H1N1感染及判断疾病的严重程度提供一定的客观依据。方法采用流式细胞仪检测24例甲型H1N1流感患者和24名健康者外周静脉血Th1、Th2细胞因子,对结果进行统计学分析。结果 H1N1甲流患者与健康对照组相比,IL-6、IL-10水平差异有统计学意义(P<0.05),IL-2I、L-4、TNF-α和IFN-γ差异无统计学意义(P>0.05);重症组与一般患病组比较IL-6水平差异有统计学意义(P<0.05),IL-2I、L-4I、L-10、TNF-α、IFN-γ水平差异无统计学意义(P>0.05)。结论与健康者相比,甲型流感患者的Th2型细胞因子水平显著升高,IL-6、IL-10,特别是IL-6可能在流感发病中发挥作用。     

Innate and adaptive immune responses to herpes simplex virus

Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in vitro and in vivo. Cell types such as NK cells and pDCs contribute to innate anti-HSV responses in vivo. Finally, the adaptive response includes both humoral and cellular components that play important roles in antiviral control and latency. This review summarizes the innate and adaptive effectors that contribute to susceptibility, immune control and pathogenesis of HSV, and highlights the delicate interplay between these two important arms of immunity.     

A promoter mutation in the haemagglutinin segment of influenza A virus generates an effective candidate live attenuated vaccine

Background

Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses.

Objectives

It has been shown elsewhere that mutations introduced in the non-coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A/PR/8/34 (PR8) containing a modified 3′ non-coding region of RNA segment 4 (haemagglutinin).

Methods

NIBRG-93 was generated using reverse genetics. HA protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo studies were performed to assess its suitability.

Results

NIBRG-93 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM) shows that the modified virus produces a large proportion of ‘virus-like particles’ that consist of budded cell membrane covered in HA but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge.

Conclusions

We demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.     

The impact of pre-existing influenza antibodies and inflammatory status on the influenza vaccine responses in older adults

Age-associated immune changes and pre-existing influenza immunity are hypothesized to reduce influenza vaccine effectiveness in older adults, although the contribution of each factor is unknown. Here, we constructed influenza-specific IgG landscapes and determined baseline concentrations of cytokines typically associated with chronic inflammation in older adults (TNF-α, IL-10, IL-6, and IFN-γ) in 30 high and 29 low influenza vaccine responders (HR and LR, respectively). In a background of high H3 antibody titers, vaccine-specific H3, but not H1, antibody titers were boosted in LRs to titers comparable to HRs. Pre-vaccination concentrations of IL-10 were higher in LRs compared with HRs and inversely correlated with titers of pre-existing influenza antibodies. Baseline TNF-α concentrations were positively correlated with fold-increases in antibody titers in HRs. Our findings indicate that baseline inflammatory status is an important determinant for generating post-vaccination hemagglutinin-inhibition antibodies in older adults, and IgG responses can be boosted in the context of high pre-existing immunity.     

Differential immune imprinting by influenza virus vaccination and infection in nonhuman primates

Immune memory of a first infection with influenza virus establishes a lasting imprint. Recall of that memory dominates the response to later infections or vaccinations by antigenically drifted strains. Early childhood immunization before infection may leave an imprint with different characteristics. We report here a comparison of imprinting by vaccination and infection in a small cohort of nonhuman primates (NHPs). We assayed serum antibody responses for binding with hemaglutinnins (HAs) both from the infecting or immunizing strain (H3 A/Aichi 02/1968) and from strains representing later H3 antigenic clusters (“forward breadth”) and examined the effects of defined HA mutations on serum titers. Initial exposure by infection elicited strong HA-binding and neutralizing serum antibody responses but with little forward breadth; initial vaccination with HA from the same strain elicited a weaker response with little neutralizing activity but considerable breadth of binding, not only for later H3 HAs but also for HA of the 2009 H1 new pandemic virus. Memory imprinted by infection, reflected in the response to two immunizing boosts, was largely restricted (as in humans) to the outward-facing HA surface, the principal region of historical variation. Memory imprinted by immunization showed exposure to more widely distributed epitopes, including sites that have not varied during evolution of the H3 HA but that yield nonneutralizing responses. The mode of initial exposure thus affects both the strength of the response and the breadth of the imprint; design of next-generation vaccines will need to take the differences into account.

Antigenic exposures determine the acquisition and development of adaptive immunity. The humoral response in a naive individual yields both antibody-secreting plasma cells that recognize the new antigen and memory B cells that can respond to future encounters with related antigens. The combination of these two components can confer long-lasting protection against antigenically stable pathogens. For antigenically diverse pathogens and those that evolve to evade immune pressure (e.g., influenza virus and HIV), serum responses often confer incomplete immunity to future variants (1, 2).The hemagglutinin (HA) and neuraminidase (NA) define the serotype of an influenza virus isolate (3). Antigenic shifts occur when novel animal influenza viruses can transmit to humans, spread rapidly, and initiate pandemics, owing to absence of any preexisting immunity (4, 5). Historically, the descendants of pandemic viruses have become endemic seasonal variants that undergo antigenic drift as they evolve over time to evade dominant human herd immunity (6, 7). For most adults, both processes have shaped human immunity to influenza.Immune memory causes a primary infection to impart an enduring imprint (8–11). Despite a lifetime of repeated exposures to divergent influenza viruses, the relative strength of an individual’s immune response to vaccination or infection correlates with the antigenic similarity of the vaccine or infecting strain to that person’s initial exposure. Until recently, the first encounter was invariably an infection. Because of recent changes in vaccine policy in the United States and Europe, infants and toddlers are now encouraged to receive influenza vaccines before they experience an influenza infection (12, 13). We have little information, however, about the immunological memory to influenza virus established when the primary exposure is vaccination rather than infection.Using nonhuman primates (rhesus macaques) as a model, we have examined how the mode of influenza exposure affects both primary and secondary antibody responses. We found that an initial exposure by infection elicited strong, strain-specific, HA-binding, and neutralizing serum antibody responses. Initial exposure by immunization with the HA protein from the strain used in the infection arm of the study elicited relatively weaker HA-binding responses that lacked neutralization potency but had greater interseasonal forward breadth. Subsequent exposures, by immunization, generated antibodies with increased interseasonal breadth in infected animals and neutralizing activity in the initially immunized monkeys. Initially infected macaques maintained responses that were strongly imprinted by the infecting strain, while those initially immunized with protein retained a serum repertoire that cross-reacted with heterologous HAs. Moreover, the distribution of epitopes bound by serum IgG was different in the two cases. These data suggest that the mode of HA exposure influences its immune imprint and that next-generation vaccine design will need to take this influence into account.     

Efficacy of a heterologous vaccine and adjuvant in ferrets challenged with influenza virus H5N1

Please cite this paper as: Vela et al. (2012) Efficacy of a heterologous vaccine and adjuvant in ferrets challenged with influenza virus H5N1. Influenza and Other Respiratory Viruses 6(5), 328–340. Background In 1997, highly pathogenic avian influenza (HPAI) viruses caused outbreaks of disease in domestic poultry markets in Hong Kong. The virus has also been detected in infected poultry in Europe and Africa. Objective The objective of this study was to determine the efficacy of a heterologous vaccine administered with and without the aluminum hydroxide adjuvant in ferrets challenged with HPAI (A/Vietnam/1203/04). Methods Animals in four of the five groups were vaccinated twice 21 days apart, with two doses of a heterologous monovalent subvirion vaccine with or without an aluminum hydroxide adjuvant and challenged with a lethal target dose of A/Vietnam/1203/04. Results All animals vaccinated with the heterologous vaccine in combination with the aluminum hydroxide adjuvant survived a lethal challenge of A/Vietnam/1203/04. Four of the eight animals vaccinated with 30 μg of the vaccine without the adjuvant survived, while two of the eight animals vaccinated with 15 μg of the vaccine without the adjuvant survived. None of the unvaccinated control animals survived challenge. Additionally, changes in virus recovered from nasal washes and post‐mortem tissues and serology suggest vaccine efficacy. Conclusions Altogether, the data suggest that the heterologous vaccine in combination with the aluminum hydroxide adjuvant offers maximum protection against challenge with A/Vietnam/1203/04 when compared to the unvaccinated control animals or animals vaccinated without any adjuvant.     

A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort

Please cite this paper as: Kersun et al. (2013) A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort. Influenza and Other Respiratory Viruses 7(6), 1158–1167. Background:  Pediatric oncology patients represent a cohort of individuals uniquely at risk of complications from influenza, yet less likely to respond to the vaccine. It is not yet clear how to best protect this vulnerable population. Methods:  We performed a prospective analysis of 177 pediatric oncology patients to define the predictors of influenza vaccine responses. Each variable was examined over three time points and a repeated measure analysis was performed. Results:  Patients with ALL vaccinated during induction phase had superior influenza vaccine responses than those subjects vaccinated during post‐induction or maintenance phases (P = 0·0237). Higher aggregate HAI titer responses were associated with a higher baseline B‐cell count (P = 0·0240), and higher CD4 and CD8 influenza‐specific T‐cell responses, suggesting prior antigen exposure is a significant contributor. The solid tumor cohort had equivalent responses during all time frames of chemotherapy. Discussion:  The optimal protection from influenza of pediatric patients on chemotherapy should include vaccination, but it is clear that not all patients produce high titers of antibodies after vaccination. This study identified biomarkers that could be used to individualize vaccine approaches. Immunologic predictors might have a role in targeting resources, as B‐cell counts predicted of vaccine responses among the patients with ALL.     

A comparison of cellular and humoral immune responses to trichuroid derived antigens in human trichuriasis

Individuals, residing in a region highly endemic for Trichuris trichiura, were examined for cytokine and proliferative responses to T. trichiura worm homogenate (TtAg), T. trichiura excretory/secretory products (TtES) and the equivalent antigenic preparations from the murine whipworm, Trichuris muris. Serum antibody levels against TtAg, T. muris worm homogenate and T. muris ES products were also studied. Measurable levels of immunoglobulin (Ig)G1, IgG4, IgA and IgE against T. muris antigens were detected, indicating a degree of conservation of epitopes between antigens derived from both species. Although levels of interleukin (IL)-4, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and proliferative responses produced were comparable between homogenate antigens of either species and ES antigens of either species, a markedly different cellular response was observed in cultures stimulated with homogenate antigens compared to ES antigens. ES antigens preferentially induced IL-10 (P > 0.001) and TNF-alpha (P > 0.001) production, whereas levels of IL-4 (P > 0.001), IL-13 (P > 0.001) and proliferative responses (P > 0.001) were greater in cultures stimulated with whole worm extracts. Our findings suggest that T. muris preparations could be used as an alternative to T. trichiura proteins as a source of antigens in ex vivo cultures and that ES products stimulate a distinct immune response compared to somatic antigens.