Cellular response in humans following vaccination with gripax influenza virus

Cellular response of peripheral blood lymphocytes to influenza antigens was measured in a group of young nurse-student volunteers (17–24 years old), following vaccination with a formol-inactivated trivalent influenza vaccine (Gripax). Cord blood lymphocytes (controls) did not react with any of the antigens. This excluded the possibility of any nonspecific mitogenicity of viral antigens. Viability of the cells was indicated by their responsiveness to phytohemagglutinin (PHA). Prior to immunization antigenic recognition to circulating strains (A/England (H₃N₂) and B/Hong Kong) was found in about 44% of the vaccinees; recognition of the recent strain A/USSR (H₁N₁) was found in only 10.5%. Following vaccination, approximately 80% of the subjects exhibited cellular response to all three vaccine strains. This includes the negative subjects, who showed an approximate 70% rate of conversion. There was no correlation between the antibody state and cellular response prior to and following vaccination as gathered from matched data of each participant.     

Antibody reactive in antibody-dependent cell-mediated cytotoxicity following influenza virus vaccination

The antibody reactive in antibody-dependent, cell-mediated cytotoxicity (ADCC) to influenza virus-infected cells was measured in two groups of seven volunteers each, before and after immunization with inactivated or live attenuated A/Victoria/3/75 influenza virus vaccines. Age-matched controls were seven adult individuals who experienced natural influenza infection due to A/Victoria/3/75-like virus strain. After inactivated whole influenza virus immunization all the subjects showed a significant rise of the antibody reactive in ADCC (from a mean value of 4.7% to 17.1% cytotoxicity, before and 5 weeks after immunization, respectively) as well as of hemagglutination inhibition (HI) antibody (fourfold or greater increase). These immune responses were similar to those observed among naturally infected controls. After live attenuated virus vaccination, no significant increase in titer of antibody reactive in ADCC was detected, even though the vaccine induced significant increase of HI antibody titer. Little correlation was found between ADCC and HI antibody rises in sera of recipients of inactivated virus vaccine and of naturally infected individuals, while, in live attenuated influenza virus vaccinees, the rise of HI antibody titer did not correspond to a significant increase of ADCC antibody titer; several subjects who developed a significant rise in ADCC antibody titer did not show significant variation in antibody to neuraminidase and/or to complement fixation influenza virus antigens.     

Immune response of adults to sequential influenza vaccination

Annual immunization against influenza is recommended for numerous individuals, but the antibody response to sequential vaccination has not been well characterized. Levels of hemagglutination-inhibition antibody were measured in adults given either two or three doses of trivalent influenza vaccine at six-month intervals. A significant rise in the number of individuals with antibody titers of greater than or equal to 40 was seen for all three antigens only after initial vaccination. Repeated vaccination was necessary to maintain adequate antibody levels only to the A/Brazil (H1N1) antigen; it did not significantly affect the proportions of individuals with protective levels of antibody to either the A/Bangkok (H3N2) or the B/Singapore 222/79 antigens. These findings do not support the current recommendation for annual immunization when the vaccine formulation has not changed.     

Dynamics of HIV-1 replication following influenza vaccination of HIV+ individuals

Levels of HIV-1 have been reported to increase in peripheral blood after influenza vaccination of HIV⁺ individuals. In this study we have evaluated the dynamics of these changes. Ten HIV-1⁺ individuals classified in revised CDC clinical categories B and C as well as five seronegative healthy controls were vaccinated with the recommended influenza strains. HIV viral RNA and proviral DNA were sequentially quantified in serum and blood lymphocytes, respectively. Nine of the 10 HIV⁺ individuals had an increase in the frequency of infected CD4 cells 2 weeks after influenza vaccination. Individuals with low viral load had a rapid increase in viraemia and a small increase in frequency of infected cells in peripheral blood. In contrast, individuals with high viral load had a small drop in viraemia followed by a significant rise in the rate of infected cells. The observed changes may resemble those taking place during intercurrent infections in HIV⁺ individuals. The effects of the relative increases in infectious virus after the transient viraemic phase should be further investigated to evaluate potential risks of vaccination.     

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD

Epidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = −0·4253, P = 0·0036) and influenza B (r = −0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4⁺ T helper cells (r = −0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.     

Immune response to influenza vaccination in an elderly population

The purpose of this study was to assess the serum antibody responses to both the hemagglutinin and the neuraminidase antigens of inactivated influenza vaccine in 45 elderly and 28 younger adults. After vaccination, antihemagglutinin antibody levels increased significantly and mean fold increases ranged from 2.8 to 22.0. Seroprotection rates were between 42.2 and 91.1% 1 month after vaccination and 15.6 and 84.4% 5 months afterward. Seroresponse rates ranged from 42.2 to 91.1% 1 month after vaccination and 15.6 to 82.2% 5 months afterward. After vaccination antineuraminidase antibody levels increased significantly and mean fold increases ranged from 3.6 to 12.3. Significantly higher antibody responses to both hemagglutinin and neuraminidase were observed for antigen A(H3N2) than for antigens A(H1N1) and B. In most instances there were no statistically significant differences between the elderly and the control subjects. Influenza vaccine was immunogenic in the institutionalized elderly, who developed good antibody responses to influenza hemagglutinin and neuraminidase antigens.     

Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus

The effect of a fish oil diet on virus-specific cytotoxicity and lymphocyte proliferation was investigated. Mice were fed fish oil (17 g fish oil and 3 g sunflower/100 g) or beef tallow (17 g tallow and 3 g sunflower/100 g) diets for 14 days before intranasal challenge with influenza virus. At day 5 after infection, lung virus-specific T lymphocyte, but not macrophage or natural killer (NK) cell, cytotoxicity was significantly lower in mice fed fish oil, while bronchial lymph node cell proliferation to virus was significantly higher. In mice fed fish oil, spleen cell proliferation to virus was also significantly higher following immunization. The results showed that, despite improved lymphocyte proliferation, fish oil impairs primary virus-specific T lymphocyte cytotoxicity. This impairment may explain the delayed virus clearance that we have previously reported in infected mice fed the fish oil diet.     

Acute transverse myelitis following vaccination against H1N1 influenza: a case report

H1N1 vaccination is currently safe, and only rare acceptable side-effects have been reported. Here we describe for the first time a serious adverse event, i.e., acute transverse myelitis, following H1N1 vaccination in China. After the standard treatment with methylprednislone, the patient recovered completely.     

Healthcare workers and influenza vaccination: an ERS-ESCMID Web-based survey

We performed a Web-based survey on attitudes and uptake of H1N1 influenza vaccination among members of two European societies, namely the European Respiratory Society and the European Society of Clinical Microbiology and Infectious Diseases. A multidisciplinary panel developed a questionnaire that examined physicians’ and members’ knowledge, attitudes and practice about seasonal and pandemic (H1N1) influenza vaccination. In all, 1334 healthcare workers from 83 countries (785 men and 549 women, mean age 45 ± 7 years) accessed and completed the survey. Safety concerns about vaccines was the main reason reported by 451/1285 respondents for not being vaccinated. More than 30% of 1282 respondents considered the management of communication on the flu pandemic by health authorities to be insufficient. The results of this survey should help health authorities to better design future steps for the successful vaccination of healthcare workers.     

Clinical and serological response in humans following immunization with gripax influenza vaccine

A commercial trivalent formol-inactivated influenza vaccine (Gripax) was tested. The vaccine consisted of equal amounts of A/England/321/77 (H₃N₂), B/Hong Kong/8/73, and A/USSR/99/177 (H₁N₁) strains. One hundred four females were injected intramuscularly. Eighty-eight (74.6%) were 17–24 yr old and 16 (15.4%) were 29–45 yr old. Seventy subjects were immunized with 1,200 IU, 24 with 1,680 IU, and 10 with 2,400 IU. A follow-up for adverse side effects was carried out during 72 hr following vaccination. There was no absence from work or school, nor did the subjects develop any systemic symptoms (fever and malaise). Local reactogenic effects were minor and included painless erythema and induration of low degree, which were observed in small numbers of the recipients and lasted for no more than 24–48 hr. Localized, axillary lymphadenopathy was noted in one subject. Seventy-four paired sera samples were tested for hemagglutination inhibition (HI) response. A highly reactive response to A/England and B/Hong Kong strains was observed, as evidenced by an at-least fourfold increase of titers. There was no significant change when a dose of 400 IU or more was given: An 83.6% and 89.4% response was, respectively, recorded for A/England and 69.0% and 73.6%, respectively, for B/Hong Kong. However, when the dose of A/USSR was increased, the response was significantly elevated from 56.0 to 84.2%. All the sera tested for neuraminidase inhibition antibody showed a satisfactory response. Regardless of the dose, a single administration of the vaccine sufficed to confer a high degree of immunity against the “old” circulating strains: 94–100% against A/England and 79–90.9% against B/Hong Kong. Immunization with 400 IU of the recent strain A/USSR conferred immunity in 50.9% of the cases, whilc the administration of a dose equal to or larger than 560 IU elicited a far higher rate of immunity-89.4%. The high quality of the vaccine is evidenced by the conversion rate from nonimmune to the immune state, as well as by the lack of undesirable side effects.     

Age-dependent antibody response in mice and humans following oral influenza immunization

In order to compare the antibody response in serum and secretions from healthy young subjects and the elderly (>60 years), volunteers were immunized with the commercial inactivated influenza virus vaccine, by the usual (parenteral) route or orally. Also, young and old mice (mean age, 20 months) were orally immunized with live influenza virus. The older mice responded with a very slight rise in their serum and respiratory tract antibody levels compared with the young mice but showed no diminution in protection against lethal viral challenge. Elderly volunteers showed only slight serum antibody responses after parenteral immunization compared with the young. Neither group demonstrated a rise in serum antibody following oral immunization. With respect to the secretory IgA (SIgA) antibody response, certain differences were noted between the young and the elderly: the preimmunization levels of antibody to influenza virus were significantly greater in nasal secretions and saliva in the elderly as compared to the young volunteers, and the salivary antibody response was diminished in the elderly. This lack of a salivary antibody response in the elderly was explicable by the inverse relationship between the preimmunization SIgA antibody titers and the response to immunization. Oral immunization led to no more side effects than observed in the placebo control group.     

Parental reasons for non-uptake of influenza vaccination in young at-risk groups: a qualitative study

Background

Uptake rates of influenza vaccination in young at-risk groups in primary care (UK) are known to be poor.

Aim

To explore parental reasons for non-uptake of influenza vaccination in young at-risk groups. The study hypothesis was that exploration of parental reasons for non-uptake may reveal important barriers to an effective influenza vaccination programme.

Design and setting

Thematic analysis of a questionnaire survey with interview follow-up at a single general practice in Inverness, Scotland.

Method

Parents of children identified as being in an at-risk group for influenza vaccination but who had not received vaccination were sent questionnaires and offered the opportunity to take part in a follow-up interview.

Results

Several key themes emerged, including uncertainty about the indication for vaccination, issues of choice, challenges with access, lack of parental priority, and issues relating to health beliefs.

Conclusion

Any attempt to improve the vaccination rate needs to address the range of decision-making processes undertaken by parents and children. Better and more tailored information and educational delivery to parents, patients, and healthcare providers may lead to an increase in the rates of influenza vaccination uptake in at-risk children. Access is a barrier described by some parents.     

Mendelian randomization suggests a potential causal effect of eosinophil count on influenza vaccination responsiveness

Currently, the clinical factors affecting immune responses to influenza vaccines have not been systematically explored. The mechanism of low responsiveness to influenza vaccination (LRIV) is complicated and not thoroughly elucidated. Thus, we integrate our in-house genome-wide association studies (GWAS) analysis result of LRIV (N = 111, Ncase [Low Responders] = 34, Ncontrol [Responders] = 77) with the GWAS summary of 10 blood-based biomarkers (sample size ranging from 62 076−108 794) deposited in BioBank Japan (BBJ) to comprehensively explore the shared genetics between LRIV and blood-based biomarkers to investigate the causal relationships between blood-based biomarkers and LRIV by Mendelian randomization (MR). The applications of four MR approaches (inverse-variance-weighted [IVW], weighted median, weighted mode, and generalized summary-data-based MR [GSMR]) suggested that the genetically instrumented LRIV was associated with decreased eosinophil count (β = −5.517 to −4.422, p = 0.004−0.039). Finally, we conclude that the low level of eosinophil count is a suggestive risk factor for LRIV.     

Lymphocyte blastogenic responses to influenza virus antigens after influenza infection and vaccination in humans.

Virus-specific in vitro cell-mediated immune responses were investigated in 20 normal volunteers who were challenged with liver influenza A/VIC/3/75 (H3N2) virus and in 13 volunteers who were vaccinated with inactivated vaccine containing A/VIC and A/NJ/8/76 (HswN1) antigens. Lymphocyte cultures were established from peripheral blood samples obtained prior to and at various times after infection or vaccination. Blastogenesis was determined by [3H]thymidine incorporation after stimulation of cultures with purified, inactivated, whole influenza viruses. Six days after infection, significantly elevated levels of blastogenesis were observed after in vitro stimulation with A viruses of hemagglutinin and neuraminidase subtypes that were the same as (H3N2) or antigenically distinct from (Heq1Neq1 or HswN1) those of the challenge virus, although maximum stimulation was noted with virus of the same hemagglutinin subtype (H3) as the challenge virus. Similar although more prolonged blastogenic responses were noted in lymphocyte cultures from vaccinees who had serum antibody rises after vaccination. The kinetics of these responses suggest that cell-mediated immunity may play a role in early events after infection and vaccination with influenza virus.     

北京市实施大规模流感疫苗接种政策的伦理学讨论

北京市自2007年,对全市中小学生和老年人开展了大规模流感疫苗接种的减免政策,至2009年已实现对全市中小学生和老年人的全部免费接种。至今已累计接种了约800万人次,取得了良好的社会效果和卫生经济学效果。然而与此同时,知情同意、个人信息保密、疫苗接种事故、群体免疫屏障以及医疗废弃物等伦理学问题也日益凸显。     

A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans

1. Download : Download high-res image (140KB)
2. Download : Download full-size image

     

Lymphocyte cytotoxicity to influenza virus-infected cells: response to vaccination and virus infection

Peripheral blood leukocytes obtained from volunteers at various times following influenza vaccine or live influenza virus infection were assayed for cytotoxicity against influenza virus-infected cells. Cytotoxicity was highest on days 3 and 7 following vaccination with commercial A/Port Chalmers/1/73 inactivated influenza virus vaccine. Maximal cytotoxicity was found 9 days after infection induced by intranasal inoculation of a strain of A/Scotland/840/74 influenza virus. Individuals naturally infected with A/Victoria/3/75 were also found to have elevated cytotoxicity approximately 1 week after onset of illness. Cytotoxicity levels decreased toward base line approximately 30 days after the virus exposure. The effector mechanism(s) responsible for the early, transient elevation in specific immune release to influenza virus-infected cells may be different from the antibody-dependent cell cytotoxicity demonstrated in the peripheral blood leukocytes from volunteers who had a remote experience with influenza virus.     

Influenza vaccination in patients with asthma: why is the uptake so low?

BACKGROUND: Patients with asthma are particularly susceptible to serious complications from influenza. The Chief Medical Officer recommends annual influenza vaccination for adult patients with asthma. The uptake of influenza vaccination by patients with asthma is only 40% and, unlike other high-risk groups, has failed to increase in recent years. AIM: To investigate the contribution of sociodemographic factors, asthma morbidity, and health beliefs to influenza vaccination uptake in patients with asthma. Design of study: Cross-sectional questionnaire study. SETTING: Single urban British general practice, Exeter, UK. METHOD: A questionnaire survey was sent to adult patients with asthma. Participants were aged 16-65 years, were receiving beta(2) agonists and inhaled steroids, and had been invited for influenza vaccination in September 2003. Data were examined using univariate analysis and logistic regression. RESULTS: A total of 136/204 (66.7%) patients responded to the survey. Influenza vaccination uptake in the study population was 40%. Younger patients were less likely to have undergone vaccination than older patients. There was no difference in vaccination uptake rates between groups of patients defined by other sociodemographic factors. Asthma morbidity was similar in vaccinated and non-vaccinated groups of patients. Vaccinated individuals had a greater belief in the efficacy of the vaccination and medical advice regarding the vaccination, and felt more susceptible to influenza and its complications when compared with non-vaccinated individuals. A fear of side-effects was associated with declining the invitation for vaccination. These health beliefs were the only independent predictors of uptake of influenza vaccination among this group of patients with asthma. CONCLUSION: Improving vaccination uptake in patients with asthma is unlikely unless individual health beliefs are taken into account.