Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients.

BACKGROUND: In this study we compared the immunogenicity of influenza vaccine administered intradermally to the standard intramuscular vaccination in lung transplant recipients. METHODS: Patients were randomized to receive the trivalent inactivated seasonal 2008-9 influenza vaccine containing either 6 μg (intradermal) or 15 μg (intramuscular) of hemagglutinin per viral strain. Immunogenicity was assessed by measurement of geometric mean titer of antibodies using the hemagglutination-inhibition (HI) assay. Vaccine response was defined as a 4-fold or higher increase of antibody titers to at least one vaccine antigen. RESULTS: Eighty-five patients received either the intradermal (n = 41) or intramuscular (n = 44) vaccine. Vaccine response was seen in 6 of 41 patients (14.6%) in the intradermal vs 8 of 43 (18.6%) in the intramuscular group (p = 0.77). Seroprotection (HI ≥1:32) was 39% for H1N1, 83% for H3N2 and 29% for B strain in the intradermal group vs 28% for H1N1, 98% for H3N2 and 58% for B strain in the intramuscular group (p = 0.36 for H1N1, p = 0.02 for H3N2, p < 0.01 for B). Mild adverse events were seen in 44% of patients in the intradermal group and 34% in the intramuscular group (p = 0.38). CONCLUSIONS: Immunogenicity of the 2008-9 influenza vaccine given intradermally or intramuscularly was overall poor in lung transplant recipients. Novel strategies for influenza vaccination in this population are needed.

Improved efficiency of a Salmonella-based vaccine against human papillomavirus type 16 virus-like particles achieved by using a codon-optimized version of L1.

Cervical cancer results from cervical infection by human papillomaviruses (HPVs), especially HPV16. An effective vaccine against these HPVs is expected to have a dramatic impact on the incidence of this cancer and its precursor lesions. The leading candidate, a subunit prophylactic HPV virus-like particle (VLP) vaccine, can protect women from HPV infection. An alternative improved vaccine that avoids parenteral injection, that is efficient with a single dose, and that induces mucosal immunity might greatly facilitate vaccine implementation in different settings. In this study, we have constructed a new generation of recombinant Salmonella organisms that assemble HPV16 VLPs and induce high titers of neutralizing antibodies in mice after a single nasal or oral immunization with live bacteria. This was achieved through the expression of a HPV16 L1 capsid gene whose codon usage was optimized to fit with the most frequently used codons in Salmonella. Interestingly, the high immunogenicity of the new recombinant bacteria did not correlate with an increased expression of L1 VLPs but with a greater stability of the L1-expressing plasmid in vitro and in vivo in absence of antibiotic selection. Anti-HPV16 humoral and neutralizing responses were also observed with different Salmonella enterica serovar Typhimurium strains whose attenuating deletions have already been shown to be safe after oral vaccination of humans. Thus, our findings are a promising improvement toward a vaccine strain that could be tested in human volunteers.

Influenza vaccination in solid-organ transplant recipients.

PURPOSE OF REVIEW: We reviewed the most recent literature on solid-organ transplant (SOT) recipients regarding the clinical significance of influenza and the immunogenicity and safety of influenza vaccine in this population. RECENT FINDINGS: In SOT recipients, influenza is associated with significant graft dysfunction and even mortality. Early initiation of antiviral therapy is associated with a reduced risk for influenza-associated complications, mainly pneumonia. The main preventive strategy against influenza in SOT recipients remains the administration of yearly influenza vaccine. Although most studies have shown that influenza vaccination is safe after transplantation, impaired responses are expected in more immunosuppressed patients. A lower immunogenicity of influenza vaccine has been described in patients receiving mycophenolate and mammalian target of rapamycin inhibitors. The optimal timing of vaccination after transplant remains to be determined, although vaccination during the early posttransplant period appears to be safe. Novel vaccination strategies, such as intradermal vaccination or use of adjuvanted vaccines, have been evaluated in SOT recipients, with inconclusive results to date. SUMMARY: The administration of influenza vaccination is strongly recommended in SOT recipients and their relatives. Further research is needed for improving the immunogenicity of influenza vaccine in this population.

Rotavirus A genotype G1P[8]: a novel method to distinguish wild-type strains from the Rotarix® vaccine strain

Rotaviruses are important enteric pathogens for humans and animals. Group A rotaviruses (RV-A) are the most common agents of severe gastroenteritis in infants and young children and vaccination is the most effective method to reduce RV-A-associated diseases. G1P[8], the most prevalent RV-A genotype worldwide, is included in the RV-A vaccine Rotarix®. The discrimination between wild-type G1P[8] and vaccine G1P[8] strains is an important topic in the study of RV-A epidemiology to manage outbreaks and to define control measures for vaccinated children. In this study, we developed a novel method to segregate the wild-type and vaccine strains using restriction endonucleases. The dsRNA from the Rotarix® vaccine was sequenced and the NSP3 gene was selected as the target gene. The vaccine strain has a restriction pattern that is different than that of wild-type RV-A G1P[8] isolates after digestion with the restriction endonuclease BspHI. This pattern could be used as a marker for the differentiation of wild-type G1P[8] strains from the vaccine strain.

Narcolepsie avec cataplexie après vaccination anti-H1N1

IntroductionIt has been suggested that the H1N1 vaccine may be a trigger for the onset of narcolepsy-cataplexy, a rare disease whose autoimmune origin is suspected.ObservationsWe report two patients (a 9-year-old boy and an 18-year-old man) with severe narcolepsy-cataplexy, in whom the illness appeared within 3-4 weeks after H1N1 vaccination. In both cases, symptoms developed unusually abruptly and they presented with severe daytime sleepiness and multiple daily cataplexy attacks. Other similar cases have been recently reported associated with H1N1 vaccine.ConclusionAlthough no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.

Acute diarrhoea in a community cohort of children who received an oral rotavirus vaccine in Northeast Brazil

Rotavirus is an important cause of childhood diarrhoea. A monovalent rotavirus vaccine (Rotarix®) was introduced into the Immunization Program of Brazil in 2006. In this study, we describe the incidence and burden of disease of rotavirus diarrhoea in two cohorts of children (vaccinated and unvaccinated). We followed two groups of 250 children under one year old, who were enrolled in December 2006 from a low-income residential area in Northeast Brazil. The children were monitored every two weeks for two years. Stool samples from children with diarrhoea were examined for the presence of rotavirus. Rotaviruses were genotyped using real time-polymerase chain reaction. The mean numbers of all-cause diarrhoea episodes/child (adjusted for age) in the first year were 0.87 and 0.84, in vaccinated and unvaccinated children, respectively. During the second year, the number of episodes/child decreased to 0.52 and 0.42. Only 16 (4.9%) of 330 stool samples were rotavirus-positive (10 vaccinated and 6 unvaccinated children) and only P[4]G2 rotaviruses were identified. All-cause diarrhoea episodes were more severe in unvaccinated children in the first year of age (p < 0.05), while vaccinated children had more severe episodes 18 months after vaccination. Rotavirus diarrhoea incidence was very low in both groups.

Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America : a review

Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject.

Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03-adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity of the vaccines in health professionals from a Clinical Research Institute in Rio de Janeiro, Brazil and there were no serious adverse events following immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva-lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI 95%: 2.62-4.48, respectively]; however, there was no difference between the vaccines in the assessments conducted at seven and 21 days post-vaccination. The group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29-6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We concluded that the two types of vaccines caused no serious AEFI in the studied population and the adjuvanted vaccine was more reactogenic, particularly in the 24 h following vaccination. This behaviour must be confirmed and better characterised by longitudinal studies in the general population.

Brazilian hepatitis B vaccine: a six-year follow-up in adolescents

The protective anti-HBs titres were examined six-year post-immunisation with the Brazilian recombinant hepatitis B vaccine. After the primary vaccination, all adolescents (n = 89) responded with protective anti-HBs titres and had a geometric mean titre (GMT) of 4031.8 mIU/mL. In 2010, 94.5% maintained protective anti-HBs (> 10 mIU/mL) antibodies, with a GMT of 236.0 mIU/mL. A positive correlation was observed between the anti-HBs titres after the primary vaccination and the titres at the six-year follow-up (p < 0.01). Eleven subjects showed anti-HBs titres suggestive of a natural booster. Prostitution and tattoos/piercings were marginally associated with natural boosters in the multivariate analysis. This study showed the first data on anti-HBs persistence following the Brazilian hepatitis B vaccine in sexually active individuals and highlights its effectiveness in the medium term.

The potential for vaccination in leprosy elimination: new tools for targeted interventions

Despite the huge effort and massive advances toward the elimination of leprosy over the last two decades, the disease has proven stubborn; new case detection rates have stabilised over the last few years and leprosy remains endemic in a number of localised regions. The American Leprosy Missions and Infectious Disease Research Institute have undertaken a large research effort aimed at developing new tools and a vaccine to continue the push for leprosy elimination. In this paper, we outline our strategy for the integration of rapid diagnostic tests and lab-based assays to facilitate the detection of early or asymptomatic leprosy cases, as well as the efficient and focused implementation of chemoprophylaxis and immunisation to intervene in leprosy development and transmission.

Influence of Bacille Calmette-Guérin vaccination on size of tuberculin skin test reaction : to what size ?

RESUME Le diagnostic d'infection tuberculeuse repose essentiellement sur le test tuberculinique (test de Mantoux). Cependant, le résultat de ce dernier est également influencé par d'autres facteurs, le plus important étant la vaccination par le Bacille Calmette-Guérin (BCG), interaction connue depuis de nombreuses années. Il est généralement admis que l'effet de la vaccination peut entraîner des réactions positives jusqu'à un diamètre d'induration de 15 mm. Au-delà, la positivité du test est en général attribuée à une primo-infection tuberculeuse. Peu d'études se sont réellement penchées sur le sujet. Chez le personnel de soins soumis à des Mantoux répétés, cette notion revêt une importance particulière pour interpréter correctement une réaction fortement positive en l'absence de facteurs de risque tuberculeux, dans un pays à faible endémie tuberculeuse. Notre étude a cherché à déterminer si le diamètre transversal de l'induration du Mantoux était un critère fiable pour distinguer une positivité associée à une infection tuberculeuse de celle associée à une ancienne vaccination. Elle s'est attachée à rechercher un seuil au-delà duquel l'infection tuberculeuse pourrait être considérée comme probable. Entre janvier 1991 et mars 1998, tous les nouveaux employés du CHUV ont été invités à recevoir un test tuberculinique à l'occasion de leur visite d'entrée à la Médecine du personnel. En cas de réponse négative, un deuxième test a été pratiqué une semaine plus tard, pour détecter un éventuel effet booster. Lors de la première visite, l'infirmière a rempli un questionnaire comprenant les données démographiques usuelles, des informations concernant les facteurs pouvant influencer la positivité du test, notamment les antécédents de vaccination par le BCG, les expositions à la tuberculose et l'existence d'antécédents d'infection tuberculeuse. Parmi les 5117 sujets inclus dans l'étude, nous avons trouvé que l'influence de la vaccination variait en fonction de l'âge. Chez les sujets de moins de 40 ans, la vaccination par le BCG était le prédicteur le plus important d'un Mantoux positif inférieur à 18 mm, de loin supérieur aux facteurs de risque habituels pour une infection tuberculeuse, eux aussi significatifs. L'effet du BCG était présent pour des réactions allant jusqu'à 20 mm. Pour les Mantoux supérieurs à 20 mm, l'odds ratio (OR) relatif au BCG demeure clairement élevé (supérieur à 3,4) bien que non significatif. Par contre, pour les employés âgés de plus de 40 ans, le BCG est un facteur prédictif pour les tests supérieurs à 10 mm (OR 2.4) mais n'est plus un facteur significatif pour une taille supérieure à 15 mm. Ces résultats montrent que l'interprétation d'un test tuberculinique même fortement positif, doit être faite avec prudence et discernement. En effet, notre étude démontre que chez les sujets vaccinés de moins de 40 ans, dans les zones de faible endémie tuberculeuse particulièrement en l'absence de facteurs de risque pour une infection tuberculeuse, un Mantoux positif jusqu'à 18 mm est dû, le plus probablement, à une ancienne vaccination par le BCG, plutôt qu'à une infection par M tuberczilosis. L'interprétation des Mantoux de taille inférieure à 18 mm et les Mantoux effectués chez des sujets de moins de 40 ans, doit prendre en compte l'existence d'un BCG antérieur. En conséquence, la mise en évidence d'une réaction de Mantoux fortement positive ne devrait pas conduire systématiquement à un traitement préventif. L'absence de spécificité du test Mantoux, utilisé pour le dépistage de la tuberculose depuis bientôt une centaine d'année, est un problème connu. Nous démontrons que la taille de l'induration ne peut pas être utilisée de façon fiable comme critère pour identifier une infection tuberculeuse chez une personne vaccinée avec le BCG, avec le risque de sui-traiter un nombre important de sujets. Dans notre étude, 21% des sujets avaient un Mantoux supérieur ou égal à 15 mm et auraient dû être traités selon les recommandations en vigueur en Suisse si l'on ne tenait pas compte du BCG antérieur. Des tests plus spécifiques sont actuellement à l'étude et permettront vraisemblablement, à l'avenir, de palier au problème de l'absence de spécificité du test de Mantoux. Abstract : Background. Previous bacillus Calmette-Guerin (BCG) vaccination can confound the results of a tuberculin skin test (TST). We sought to determine a cutoff diameter of TST induration beyond which the influence of BCG vaccination was negligible in evaluating potential Mycobacterium tuberculosis infection in a population of health care workers with a high vaccination rate and low incidence of tuberculosis. Methods. From 1991 through 1998, all new employees at the University Hospital of Lausanne, Switzerland, underwent a 2-step TST at entry visit. We also gathered information on demographic characteristics, along with factors commonly associated with tuberculin positivity, including previous BCG vaccination, history of latent M. tuberculosis infection, and predictors for M. tuberculosis infection. Results. Among the 5117 investigated subjects, we found that influence of BCG vaccination on TST results varied across categories of age (likelihood ratio test, 0.0001). Prior BCG vaccination had a strong influence on skin test results of mm in diameter among persons <40 years old, compared with the influence of factors predictive of M. tuberculosis infection. Prior latent M. tuberculosis infection and travel or employment in a country in which tuberculosis is endemic also had significant influences. Conclusions. Interpretation of TST reactions of mm among BCG-vaccinated persons <40 years of age must be done with caution in areas with a low incidence of tuberculosis. In such a population, except for persons who have never been vaccinated, TST reactions of ---518 mm are more likely to be the result of prior vaccination than infection and should not systematically lead to preventive treatment.

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

Vaccination against human papillomavirus in Switzerland: simulation of the impact on infection rates.

OBJECTIVES: Human papillomavirus (HPV) is a sexually transmitted infection of particular interest because of its high prevalence rate and strong causal association with cervical cancer. Two prophylactic vaccines have been developed and different countries have made or will soon make recommendations for the vaccination of girls. Even if there is a consensus to recommend a vaccination before the beginning of sexual activity, there are, however, large discrepancies between countries concerning the perceived usefulness of a catch-up procedure and of boosters. The main objective of this article is to simulate the impact on different vaccination policies upon the mid- and long-term HPV 16/18 age-specific infection rates. METHODS: We developed an epidemiological model based on the susceptible-infective-recovered approach using Swiss data. The mid- and long-term impact of different vaccination scenarios was then compared. RESULTS: The generalization of a catch-up procedure is always beneficial, whatever its extent. Moreover, pending on the length of the protection offered by the vaccine, boosters will also be very useful. CONCLUSIONS: To be really effective, a vaccination campaign against HPV infection should at least include a catch-up to early reach a drop in HPV 16/18 prevalence, and maybe boosters. Otherwise, the protection insured for women in their 20s could be lower than expected, resulting in higher risks to later develop cervical cancer.