Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission

Currently two vaccines, trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV), are licensed in the USA. Despite previous studies on immune responses induced by these two vaccines, a comparative study of the influence of prior influenza vaccination on serum antibody and B-cell responses to new LAIV or TIV vaccination has not been reported. During the 2005/6 influenza season, we quantified the serum antibody and B-cell responses to LAIV or TIV in adults with differing influenza vaccination histories in the prior year: LAIV, TIV, or neither. Blood samples were collected on days 0, 7–9 and 21–35 after immunization and used for serum HAI assay and B-cell assays. Total and influenza-specific circulating IgG and IgA antibody secreting cells (ASC) in PBMC were detected by direct ELISPOT assay. Memory B cells were also tested by ELISPOT after polyclonal stimulation of PBMC in vitro. Serum antibody, effector, and memory B-cell responses were greater in TIV recipients than LAIV recipients. Prior year TIV recipients had significantly higher baseline HAI titers, but lower HAI response after vaccination with either TIV or LAIV, and lower IgA ASC response after vaccination with TIV than prior year LAIV or no vaccination recipients. Lower levels of baseline HAI titer were associated with a greater fold-increase of HAI titer and ASC number after vaccination, which also differed by type of vaccine. Our findings suggest that the type of vaccine received in the prior year affects the serum antibody and the B-cell responses to subsequent vaccination. In particular, prior year TIV vaccination is associated with sustained higher HAI titer one year later but lower antibody response to new LAIV or TIV vaccination, and a lower effector B-cell response to new TIV but not LAIV vaccination.

/pdf/influence-of-prior-influenza-vaccination-on-antibody-and-b-5hjieuxkr9.pdf

Influence of Prior Influenza Vaccination on Antibody and B-Cell Responses

Background According to common recommendations, influenza vaccination should be performed annually. It has been suggested that vaccination in previous years reduces vaccine efficacy in the long term. Objective To determine whether the protection of influenza vaccine decreases when vaccination is repeated annually. Methods Articles published between 1966 and 1997 were selected from MEDLINE. The end point for field studies was the influenza-related morbidity or mortality during influenza outbreaks (resulting in field protection rates). The end point for serologic studies was exceeding a protective postvaccination hemagglutination-inhibition titer (serologic protection rates). Protection rate differences between groups with single and multiple vaccinations were subjected to meta-analysis. Results Seven field studies (including 13 trials) supported the hypothesis that protection in multiple-vaccination groups is at least as good as that in single-vaccination groups. Ten trials with 5117 observations could be subjected to meta-analysis. The pooled protection-rate difference was close to 0 (1.1%; 95% confidence interval, −0.2% to 2.4%), thus detecting no difference between single or multiple vaccination. Twelve serologic studies (including 53 trials) showed heterogeneous results: 9 trials were significantly in favor of single vaccination, and 7 were in favor of multiple vaccination, but in most cases, there was no significant difference between the 2 vaccination groups. The pooled serologic protection-rate difference from 52 trials (12,341 observations) was again close to 0 (1.7%; 95% confidence interval, −1.3% to 4.8%). Conclusions We did not detect any evidence for a decreasing protection with annually repeated influenza vaccination. Annual vaccination should not be discouraged in populations at risk.

/pdf/protection-against-influenza-after-annually-repeated-1adyrdtgjy.pdf

Protection against influenza after annually repeated vaccination. A meta-analysis of serologic and field studies.

Publisher Summary Immunization is the most feasible method for preventing influenza. Three types of influenza viruses circulate and cause disease in humans: A, B, and C. The only influenza virus vaccine that is currently licensed in the United States is a trivalent formalin-inactivated (TIV) preparation that includes influenza A (H3N2), influenza A (HlNl), and influenza B virus components. Immune correlates of protection have been established, and a global network is in place to monitor the appearance and circulation of the antigenic variants of influenza viruses as well as the appearance of novel subtypes of influenza A. The most promising live attenuated influenza vaccine (LAIV) candidate is the cold-adapted (ca) influenza vaccine. Experimental vaccines that elicit a mucosal antibody response and those that elicit a cellular immune response against cytotoxic T lymphocytes (CTL) epitopes present on internal proteins may provide cross-protection against antigenically drifted strains. The current formulation of the ca vaccine is a trivalent preparation comprising reassortant ca viruses bearing the (hemagglutinin) HA and neuraminidase (NA) genes of the recommended influenza A (HlN1 and H3N2) and influenza B viruses. Various future developments in vaccines, such as adjuvant vaccines, cell culture-derived vaccines, vaccines against potential pandemic strains, DNA vaccines, and genetically engineered LAIV are discussed in this chapter.

Influenza Vaccines: Present and Future

Recent outbreaks of severe acute respiratory syndrome and avian influenza demand optimized strategies to protect society from pandemic respiratory illnesses [1, 2]. Of particular concern is the population of solid organ transplant recipients. These individuals are at high risk for morbidity and mortality secondary to influenza, and their immune response to vaccination is poorly understood. Pediatric transplant recipients are, perhaps, the most vulnerable, because even immunocompetent children are susceptible to serious influenza disease [3, 4]. At the time of transplantation, infants and young children often lack prior exposure to influenza and its subsequent protective immunologic priming [5].

Pediatric solid organ transplant recipients are at risk for influenza-related complications, including pneumonia, sepsis, CNS disease, acute graft rejection, and death [6–8]. In a retrospective review involving 42 pediatric solid organ transplant recipients with influenza or parainfluenza, 3 patients with influenza died and 4 developed concurrent infections with cytomegalovirus (CMV) and bacteremia [6].

Liver transplant recipients represent a growing proportion of the population of pediatric transplant recipients. How these children respond to vaccinations, including the inactivated trivalent subvirion influenza vaccine, is poorly understood. Evaluations of the inactivated influenza vaccine in other immunocompromised populations, such as children with HIV infection and cancer, suggest a diminished response to the vaccine that is relative to immunocompetent children [9, 10]. However, the data regarding the immune response in pediatric solid organ transplant recipients are less substantial. Prior studies have yielded conflicting results, with some authors suggesting a diminished antibody response to vaccination [11–13].

The generation of serum antibodies following influenza vaccination is crucial for protection from illness and is an important correlate for vaccine efficacy [5, 14]. However, clearance of influenza and prevention of influenza-associated complications also require a vigorous cell-mediated immune response. Influenza-specific CD8+ T cells mediate the killing of infected host cells and up-regulate proinflammatory cytokines in animal models [15, 16]. Adults with baseline cytotoxic T cell immunity against influenza clear virus more effectively than those with no pre-existing cell-mediated immunity, and cytotoxic T cells may demonstrate cross-reactivity when responding to new influenza A virus subtypes [17]. Influenza in infants stimulates cytotoxic T lymphocyte proliferation, although the degree of this response may not correlate with serum hemagglutination inhibition (HI) antibody levels [18]. Following vaccination, secondary antibody response requires the expansion of memory CD8+ T cells and CD4+ T cell assistance [19–21]. Although small studies involving both pediatric hematopoietic stem cell transplant recipients and adult solid organ transplant recipients suggest a diminished T cell response to inactivated influenza vaccine [22, 23], to our knowledge, no prospective studies have evaluated this response in pediatric solid organ transplant recipients. We present the results of a single center, prospective, comparative evaluation of humoral and cell-mediated immune responses to inactivated influenza vaccine in pediatric liver transplant recipients and their healthy siblings.

A Prospective, Comparative Study of the Immune Response to Inactivated Influenza Vaccine in Pediatric Liver Transplant Recipients and Their Healthy Siblings

Annual influenza vaccination: immune response in patients over 10 years.

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Annual influenza vaccination: immune response in patients over 10 years.