Seasonal maintenance of influenza vaccine-induced antibody response in kidney transplant recipients.

BACKGROUND/AIMS: Although annual influenza vaccination is recommended for kidney transplant recipients, efficacy as reflected by serum antibody titers has not been well studied beyond 1 month in kidney transplant recipients. METHODS: We performed a single-center prospective cohort study of 51 kidney transplant recipients and 102 healthy controls receiving the 2006-2007 influenza vaccine. Anti-hemagglutinin antibody titers to A/H1N1, A/H3N2, and B were measured before and 1 month after vaccination, and again at the end of influenza season. The primary outcome was the proportion of participants maintaining seroprotection (antibody titer ≥1:32) for the duration of the influenza season after influenza vaccination. RESULTS: Median follow-up time was 175 and 155 days in the transplant and control groups, respectively. For types A/H1N1 and B, a similar high proportion of the transplant and control groups (88.5 and 81.6% vs. 83.7 and 74.2% for A/H1N1 and B, respectively) maintained seroprotection. For type A/H3N2, significantly less of the transplant group (66.7%) versus the control group (90%) maintained a protective influenza vaccine response (odds ratio 0.21, 95% confidence interval 0.07-0.64). This difference disappeared in adjusted analyses. Actual geometric mean titers decreased significantly within both groups (p < 0.001) but this did not differ between groups. CONCLUSIONS: Once they have developed protective vaccine-induced antibody responses to influenza vaccine, kidney transplant recipients are able to maintain adequate protective levels of antibody compared with healthy controls.

Decreased antibody response to influenza vaccination in kidney transplant recipients: a prospective cohort study.

BACKGROUND: Antibody response to the inactivated influenza vaccine is not well described in kidney transplant recipients administered newer, but commonly used, immunosuppression medications. We hypothesized that kidney transplant recipient participants administered tacrolimus-based regimens would have decreased antibody response compared with healthy controls. STUDY DESIGN: Prospective cohort study of 53 kidney transplant recipients and 106 healthy control participants during the 2006-2007 influenza season. All participants received standard inactivated influenza vaccine. SETTING & PARTICIPANTS: Kidney transplant recipients administered tacrolimus-based regimens at a single academic medical center and healthy controls. PREDICTOR: Presence of kidney transplant. OUTCOMES: Proportion of participants achieving seroresponse (4-fold increase in antibody titer) and seroprotection (antibody titer > or = 1:32) 1 month after vaccination. MEASUREMENTS: Antibody titers before and 1 month after vaccination by means of hemagglutinin inhibition assays for influenza types A/H1N1, A/H3N2, and B. RESULTS: A smaller proportion of the transplantation group compared with the healthy control group developed the primary outcomes of seroresponse or seroprotection for all 3 influenza types at 1 month after vaccination. The response to influenza type A/H3N2 was statistically different; the transplantation group had 69% decreased odds of developing seroresponse (95% confidence interval, 0.16 to 0.62; P = 0.001) and 78% decreased odds of developing seroprotection (95% confidence interval, 0.09 to 0.53; P = 0.001) compared with healthy controls. When participants less than 6 months from the time of transplantation were considered, this group had a significantly decreased response to the vaccine compared with healthy controls. LIMITATIONS: Decreased sample size, potential for confounders, outcome measure used is the standard but does not give information about vaccine efficacy. CONCLUSIONS: Kidney transplant recipients, especially within 6 months of transplantation, had diminished antibody response to the 2006-2007 inactivated influenza vaccine.

Antibody responses after inactivated influenza vaccine in young children.

BACKGROUND: The frequency and duration of antibody responses after trivalent inactivated influenza vaccine (TIV) in young children are not well defined and assume greater importance with the expanded recommendations for vaccine use in children aged 6 months-5 years. METHODS: Forty-three children aged 6-23 months were vaccinated with TIV in the fall of 2002. At enrollment the majority of children were seronegative to one or more of the vaccine antigens and had no previously documented influenza. Postvaccination sera were collected in the subsequent fall and winter seasons. Acute antibody responses to TIV were determined using standardized hemagglutination inhibition (HAI) and neutralization assays. In calculating the duration of responses, sequential sera were analyzed to the last available sera, to the point at which antibody became undetectable, or to intercurrent influenza infection. RESULTS: Forty-three subjects contributed 121 sera that were analyzed for HAI responses to TIV. Four-fold HAI rises after 2 doses of TIV in naive individuals were seen in 13 (72%) to H3N2, 22 (92%) to H1N1, and 15 (60%) to influenza B. Fewer 4-fold rises were seen in those with preexisting antibody. The results of microneutralization assays to H3N2 correlated well with HAI results. The time for antibody to decay to one-half of the postvaccination titer (t1/2) was approximately 126 days for H1N1 and 258 days for H3N2. CONCLUSIONS: Although not all children responded with 4-fold rises in antibody or achieved the putative protective titer of > or =1:32, the half-life of antibody suggested that children immunized in the fall should have immune responses sustained throughout the ensuing influenza season.

Duration of virus shedding after trivalent intranasal live attenuated influenza vaccination in adults.

OBJECTIVE: To characterize the probability and duration of viral shedding among adults given trivalent live attenuated influenza vaccine (LAIV). DESIGN: Prospective surveillance study. METHODS: Nasal wash samples were collected from adult volunteers at baseline and on days 3, 7, and 10 and between days 17 and 21 following intranasal LAIV vaccination. The presence, titer, and identification of each specific strain of influenza virus shed were determined by standard methodology. RESULTS: Twenty subjects received LAIV. No samples were positive for influenza virus at baseline. After LAIV vaccination, influenza virus was recovered from 10 of 20 vaccinees on day 3, from 1 of 18 vaccinees on day 7, and from none of the samples on days 10 or 17 through 21. Vaccinees who shed vaccine virus were significantly younger than those who did not (mean age, 26.4 vs 38.6 years; P < .01). Although the presence of specific mucosal immunoglobulin A to influenza B was associated with significantly less shedding of influenza B after vaccination (P = .02), associations of shedding with other measures of immunity were not detected. CONCLUSION: The duration of shedding of vaccine virus after LAIV in adults i s limited and may be associatedwith an individual's prior influenza vaccination history.

CD154 regulates primate humoral immunity to influenza.

Current methods of immunosuppression for the purposes of allowing solid organ transplantation in humans are broadly inhibitory and thus are associated with an increased risk of opportunistic infections and neoplasia. We have shown previously that a selective blockade of CD40-CD154 interactions during heart transplantation in cynomolgus macaques significantly delays immune-mediated graft injury. Here, we determined the effect of anti-CD154 mAb therapy on primate serologic responses to immunization with influenza virus hemagglutinin (HA), a T-cell-dependent Ag. We found that CD154 blockade attenuated primary and secondary serum Ab responses of IgM and IgG isotypes to influenza, even when anti-CD154 treatment was discontinued prior to reimmunization. These findings show that in primates CD40-CD154 interactions are necessary for both primary and secondary Ab responses to viral Ags. Furthermore, the data suggest that viral Ag stimulation of primates in the absence of CD154 stimulation may have a tolerizing effect on that Ag.

Detection of mucosal antibodies in HIV type 1-infected individuals.

HIV-1-specific mucosal IgA antibodies may correlate with protection in highly exposed but uninfected individuals, but have been detected at highly variable levels in HIV-1-infected individuals. To determine the best assays for detection of IgA antibodies in mucosal samples, rectal washes from 16 HIV-1-infected and 14 uninfected individuals were distributed to six laboratories experienced in detection of mucosal antibodies. Assays for HIV-1-specific IgA and IgG were performed in a blinded fashion by each of the laboratories using modifications of ELISA and chemiluminescence-enhanced Western blotting. Rectal washes contained easily detectable total IgA levels that did not differ between HIV-1-infected and uninfected groups. Irrespective of the assay used, HIV-1-specific IgA antibodies were absent in most samples; only one laboratory identified a higher frequency of positive samples from HIV-1-infected than uninfected individuals. In spite of 10-fold lower levels of total IgG than IgA, all but one laboratory identified HIV-1-specific IgG in most rectal washes of HIV-1-infected individuals. Comparable and readily detectable levels of influenza-specific IgA antibodies were present in nasal, salivary, and rectal secretions from both HIV-1-infected and uninfected individuals. These observations suggest a selective alteration in the production of HIV-1-specific IgA antibodies in HIV-1-infected individuals.