Lidia B. Brydak

Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination: an impact of immunosenescence

We assessed association between prior cytomegalovirus (CMV) infection, proinflammatory status and effectiveness of the anti-influenza vaccination. We examined 154 individuals during the epidemic season dividing them according to the age, response to the vaccine and the Senieur Protocol (SP). The anti-hemagglutinins (HI), tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6, IL10, ACTH/cortisol axis, anti-CMV antibodies and CD28+CD57- lymphocytes were assessed. Non-responders of both ages we characterised by higher levels of anti-CMV IgG and higher percentages of CD57+CD28- lymphocytes (known to be associated with CMV carrier status) together with increased concentrations of TNFalpha and IL6 and decreased levels of cortisol. The anti-influenza vaccine induced increase in TNFalpha and IL10 in the all non-responders, while cortisol increased only in the young. Concluding, CMV carrier status eliciting elevated proinflammatory potential could contribute to unresponsiveness to the anti-influenza vaccine.

Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study

AIMS To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease (CAD). METHODS AND RESULTS Randomized, double-blind, placebo controlled study. We included 658 optimally treated CAD patients; 477 men, mean age 59.9+/-10.3 years. Three hundred and twenty-five patients received the influenza vaccine, and 333 patients placebo. Median follow-up was 298 (interquartile range 263-317) days. Primary endpoint was the cardiovascular death. Its estimated 12-month cumulative event rate was 0.63% in the vaccine vs. 0.76% in controls (HR 1.06 95% CI: 0.15-7.56, P = 0.95). There were two secondary composite endpoints: (i) the MACE (cardiovascular death, myocardial infarction, coronary revascularization) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87%, respectively (HR 0.54;95% CI: 0.24-1.21, P = 0.13). (ii) Coronary ischaemic event (MACE or hospitalization for myocardial ischaemia) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97% in controls (HR 0.54; 95% CI: 0.29-0.99, P = 0.047). CONCLUSION In optimally treated CAD patients influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events. Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality. (ClinicalTrials.gov: NCT 00371098).

Humoral immune response to influenza vaccination in patients from high risk groups.

Influenza is one of the most common respiratory diseases. Infections caused by this virus may be very serious and can lead to severe complications. So far, the most effective method of protection against influenza is annual vaccination. The Advisory Committee on Immunisation Practices recommends vaccination against influenza for some groups of people. Unfortunately, in spite of these clear indications, a large number of patients are not vaccinated.This article reviews the current scientific literature on immunological response to influenza vaccination in patients who are at especially high risk for serious post-influenza complications and for whom immunisation against this virus is strongly recommended. Results of studies carried out in Poland and other countries in elderly people, in patients with pulmonary diseases, renal diseases, diabetes mellitus, cancer and haemophilia, and in those with HIV infection are presented. In this review, we focus on the immune response to haemagglutinin. There are some discrepancies between the results of studies carried out by different authors in high risk groups of patients. Some investigations indicated poorer humoral response to influenza vaccine in these groups, while others showed responses comparable to those in healthy individuals. These differences may be explained by differences in types and stages of the chronic diseases, in the treat-ment and composition of influenza vaccines, and also patients’ ages, vaccination history and prevaccination antibody titres. Influenza vaccines are well tolerated in high risk patients, and all adverse reactions are generally mild and similar to those observed in healthy people. Although, in some cases, immunological responses to influenza vaccination measured in the whole study group were poor, there were some individual patients who, after vaccination, developed antihaema-glutinin antibody titres which are considered to give protection against the infection or contribute to a milder course of the disease.

Immune consequences of the spontaneous pro-inflammatory status in depressed elderly patients.

INTRODUCTION The aim of the study was to describe the interrelationship between senescence, depression, and immunity. METHODS We assessed 10 elderly patients with depression and 10 age- and sex-matched controls: before, at one and at six month intervals after the anti-influenza vaccination. Levels of TNFalpha, IL6, ACTH, and cortisol, titres of anti-hemagglutinins and anti-neuraminidases, lymphocytes secreting IFNgamma, IL2, IL4, and IL10, cytotoxicity of NK and CD3+ CD8+ IFNgamma+ cells, anti-CMV antibodies, and CD28- CD57+ lymphocytes known to be associated with the CMV carrier status were evaluated. RESULTS Higher levels of anti-CMV, higher percentage of the CD28- CD57+ cells, and elevated levels of TNFalpha, IL6, and cortisol concomitant with decreased levels of ACTH and insufficient production of IL10 (which increased the IFNgamma+ /IL10+ ratio) were found in the patients suffering from depression, in comparison to healthy controls. The subjects with depression revealed a low NK cytotoxicity, while a level of CD3+ CD8+ IFNgamma+ cells was comparable between the groups. Although the levels of anti-hemagglutinins and anti-neuraminidases were low in the depressed patients, they reached the protective titres. The majority of these differences disappeared when CMV titres were entered into the analyses as a covariate. DISCUSSION The results suggest that the elderly depressed patients were characterised by increased exposure to CMV in the past, which could have resulted in a pro-inflammatory profile demonstrated as elevated levels of TNFalpha, IL6 and deficiency of suppressive IL10+ cells. These changes negatively affect humoral and innate response in the depressed patients.

Immunogenicity of subunit trivalent influenza vaccine in children with acute lymphoblastic leukemia

BACKGROUND The aim of this study was to assess humoral response to influenza vaccine in children with acute lymphoblastic leukemia. METHODS Studies were performed in 25 patients previously vaccinated against influenza (Group A) and in 20 children who had never been immunized before (Group B). In Autumn, 1996, they were vaccinated with subunit trivalent influenza vaccine containing 15 microg of hemagglutinin of A/Singapore/6/86, A/Wuhan/359/95 and B/Beijing(184/93. Antihemagglutinin (HI) and antineuraminidase antibody titers were determined before immunization and 3 weeks and 6 months after vaccination by the hemagglutinin inhibition test and the neuraminidase inhibition test. All results were presented as the geometric mean titer of antibodies, mean fold increase of antibody titer, protection rate and response rate. RESULTS In Group A mean fold increase of HI antibodies ranged from 17.2 to 26.7 three weeks after vaccination and from 22.1 to 38.2 six months after vaccination, while in Group B it ranged from 15.7 to 22.6 and from 30.3 to 39.3, respectively. In the case of neuraminidase, mean fold increases for Group A varied from 9.2 to 13.2 three weeks after immunization and from 15.6 to 21.1 six months after vaccination, whereas for Group B they varied from 5.5 to 8.3 and from 14.4 to 23.4, respectively. Six months after vaccination the proportion of subjects with HI antibodies > or = 1:40, as well as those with at least 4-fold increase of HI antibody titers, ranged from 68 to 100% in Group A and from 90 to 100% in Group B. No vaccinated child was infected with the influenza virus; the vaccine was well-tolerated and did not cause any adverse reactions. CONCLUSIONS The results obtained in this study indicate that influenza vaccine is immunogenic in patients with acute lymphoblastic leukemia, despite their serious disease.

Anti-influenza vaccination in systemic lupus erythematosus patients: an analysis of specific humoral response and vaccination safety.

The objective of this study is to evaluate efficacy and safety of influenza vaccine in systemic lupus erythematosus (SLE) patients. We studied SLE patients and healthy subjects immunised with inactivated influenza vaccine. Efficacy was measured by comparing humoral response to vaccine antigens between groups. Safety was monitored by SLEDAI and serological markers. Subjects attended visits at baseline and on post-vaccination weeks 4 and 12. We enrolled 62 SLE patients and 47 healthy subjects. In post-immunisation week 4, anti-haemagglutinin antibody titres rose in the patient group at least 6.23-fold, compared to 11.90-fold among controls (P ≤ 0.05). The seroconversion rate range was 53-56% among patients and 72-85% among controls (P < 0.05 for strains H1N1 and H3N2, NS for strain type B). The seroprotection rate ranged between 62% and 73% and between 90% and 98% in the patient and control group, respectively (P < 0.05). In post-vaccination week 12, the antibody titre was higher at least 3.86-fold in the patient group and 7.65-fold among controls. The seroconversion rate range was 32-40% among patients and 64-70% among controls, while the seroprotection rate ranged between 43% and 50% and between 79% and 94%, respectively (P < 0.005 for three strains). We identified one severe and six mild to moderate SLE exacerbations by week 12. The anti-nuclear antibodies and anti-double-stranded DNA titres grew by post-immunisation week 4 (P < 0.05). The post-vaccination response was weaker in SLE patients compared to healthy subjects. Immunisation did not change underlying disease activity.

Antibody response to influenza immunization in two consecutive epidemic seasons in patients with renal diseases

The aim of this study was to assess antihemagglutinin and antineuraminidase antibody kinetics in 26 patients with renal diseases vaccinated against influenza in two consecutive epidemic seasons. Antibody responses were measured before immunization and 1, 3 and 6 months after immunization. Antihemagglutinin (HI) antibodies were determined by the hemagglutinin inhibition test and antineuraminidase (NI) antibody levels by the neuraminidase inhibition test. After vaccination HI and NI antibody titers significantly increased when compared with the pre-vaccination levels. Three months after vaccination the protection rates ranged from 50 to 61.5% in the 1995/96 season and 100% for all antigens in the 1996/97 season. Response rates ranged from 50 to 57.7% and 93.8 to 100% respectively. Significantly higher humoral response was recorded in the 1996/97 season than in the 1995/96 season. No serious adverse reactions were observed in the vaccinated patients and no symptoms of influenza or influenza-like infection were noted. In spite of some doubts about the safety and efficacy of influenza vaccination in patients from high-risk groups, the results of this study showed that many of them are able to produce HI antibodies in titers which are sufficient to protect against the influenza infection.

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.

Immunogenicity of Influenza Vaccination in Patients with Non-Hodgkin Lymphoma

Purpose: The purpose of this study was to assess humoral response to influenza vaccine in patients (pts) with non-Hodgkin lymphoma (NHL) as compared to healthy subjects (ctrl). Patients and methods: In two epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 ctrl were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in antibody titers were assessed by comparing geometric mean titers (GMT), mean fold increases (MFI), and seroprotection and seroresponse rates to baseline values. Results: Pts vaccinated in 2003/2004 had, after 1 month, increase in GMT by a factor of 8.64–26.60 for antihemagglutinin antibodies (HI) and 6.93–12.66 for antineuraminidase antibodies (NI), as compared to factor of 9.12–24.41 for HI and 4.83–10.31 for NI in ctrl. At 1 month after vaccination, seroprotection and seroresponse rates were similar in both groups, ranging from 68.42 to 84.21% and 71.93 to 94.74% in NHL, and 66.67–82.22% and 62.22–86.67% in ctrl, respectively. Pts vaccinated in 2004/2005 had increase in the GMT by a factor of 38.76–41.49 for HI and 26.59–30.31 for NI, as compared to factor of 81.19–104.32 for HI and 52.16–54.52 for NI in ctrl. Seroprotection and seroresponse rates were lower in the former group, ranging from 62.11 to 65.26% and 74.47 to 77.66%, respectively. In both seasons, pts achieved titres of antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. Conclusions: The results indicate that influenza vaccination induces sufficient immune response in pts with NHL, irrespective of previous chemotherapy.

Humoral Response to Influenza Vaccination in HIV-Infected Patients

AbstractObjective: To assess the humoral response in HIV-infected adults immunised against influenza in Poland in the epidemic season 1997/98. Patients and Methods: The study was carried out in 34 HIV-infected patients in different stages of the disease, vaccinated with a single 0.5ml dose of subunit vaccine (‘Influvac’, Solvay Pharmaceuticals BV). Antihaemagglutinin (HI) antibody levels were measured by the haemagglutinin inhibition test before immunisation and then after one and six months. Results: One month after vaccination HI antibody titres significantly increased from 1.5 to 5.5 times. After six months HI antibody levels were higher than those before vaccination and also higher than those determined one month after vaccination. Before immunisation the number of patients with HI antibody titres ≥l:40 ranged from 2.9 to 50%. After vaccination, protection rates increased and ranged from 17.6 to 79.4% one month after vaccination, and from 20.6 to 82.4% six months after vaccination. Response rate values remained at similar levels during the whole study and were between 9.4 and 14.7%. No statistically significant differences were found in humoral response between patients with different CD4 counts nor between AIDS patients and those not suffering from AIDS. Significantly higher antibody titres were recorded during the whole study for the A/Wuhan/359/95 (H3N2) influenza strain than for the A(H1N1) and B strains. Conclusions: The results of this study indicated that in HIV-infected patients humoral response to influenza vaccination was poor compared with healthy people. However, in some HIV-infected patients the vaccine induced the production of HI antibodies in titres that were considered high enough to protect against the infection.