Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec, Canada.

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.

Progress toward the global control of Neisseria meningitidis: 21st century vaccines, current guidelines, and challenges for future vaccine development.

The control of meningitis, meningococcemia and other infections caused by Neisseria meningitidis is a significant global health challenge. Substantial progress has occurred in the last twenty years in meningococcal vaccine development and global implementation. Meningococcal protein-polysaccharide conjugate vaccines to serogroups A, C, W, and Y (modeled after the Haemophilus influenzae b conjugate vaccines) provide better duration of protection and immunologic memory, and overcome weak immune responses in infants and young children and hypo-responsive to repeated vaccine doses seen with polysaccharide vaccines. ACWY conjugate vaccines also interfere with transmission and reduce nasopharyngeal colonization, thus resulting in significant herd protection. Advances in serogroup B vaccine development have also occurred using conserved outer membrane proteins with or without OMV as vaccine targets. Challenges for meningococcal vaccine research remain including developing combination vaccines containing ACYW(X) and B, determining the ideal booster schedules for the conjugate and MenB vaccines, and addressing issues of waning effectiveness.

[Adult immunisation: General points, hot topics and perspectives]. / Vaccination de l'adulte : données générales, actualités et perspectives.

Vaccination in immunocompetent adult mainly concerns booster vaccination against diphtheria, tetanus, polio and pertussis. Some chronic diseases may also require the achievement of pneumococcal and influenza vaccines. In addition, from the age of 65, annual influenza vaccination as well as one dose of a live attenuated shingles vaccine between 64 and 75 years are recommended. Immunocompromised adults, due to the increased risk of serious infections responsible of significant morbidity and mortality, are particularly concerned by vaccination. Main issues in this population are the decreased immunogenicity and efficacy of vaccination and the risk of infection with live attenuated vaccines and. Depending on the type of immunosuppression, the recommended vaccines and vaccination schemes differ. Vaccination of healthy persons caring or residing with immunocompromised patients is an important point in the vaccine strategy. The current perspectives in vaccinology concern the development of vaccines against healthcare associated infections (Clostridium difficile and Staphylococcus aureus in particular), the strategy of vaccination during pregnancy to protect new-borns (respiratory syncytial virus, group B streptococcus) and the development of new adjuvants and new routes of immunization. With the overall decline in immunization coverage and increasing distrust of vaccination, the problem of vaccine hesitancy is also a hot topic. The reasons for doubt in the vaccine usefulness and the solutions to be applied are also crucial issues.

Protecting Newborns Against Pertussis: Treatment and Prevention Strategies.

Pertussis is a potentially severe respiratory disease, which affects all age groups from young infants to older adults and is responsible for an estimated 195,000 deaths occurred globally in 2008. Active research is ongoing to better understand the pathogenesis, immunology, and diagnosis of pertussis. For diagnosis, molecular assays (e.g., polymerase chain reaction) for detection of Bordetella pertussis have become more widely available and support improved outbreak detection. In children, pertussis vaccines have been incorporated into routine immunization schedules and deployed for pertussis outbreak control. Lower levels of vaccine coverage are now being observed in communities where vaccine hesitancy is rising. Additionally, recognition that newborn babies are at risk of pertussis in the USA and UK has led to recommendations to immunize pregnant women. Among adolescents and older adults in the USA, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular pertussis (Tdap) Vaccines are recommended, but substantial individual- and system-level barriers exist that will make achieving national Healthy People 2020 targets for immunization challenging. Current antimicrobial regimens for pertussis are focused on reducing the severity of disease, reducing rates of sequelae, and minimizing transmission of infection to susceptible individuals. Continued surveillance for pertussis will be important to identify opportunities for reducing young infants' exposure and reducing the impact of outbreaks among school-aged children. Laboratory-based surveillance for newly emerging strains of B. pertussis will be important to identify strains that may evade protection elicited by currently available vaccines. Efforts to develop new-generation pertussis vaccines should be considered now in anticipation of vaccine development programs, which may require ten or more years to deliver a licensed vaccine.

Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network's variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.

The present and future of tuberculosis vaccinations.

The clinical, social, and economic burden of tuberculosis (TB) remains high worldwide, thereby highlighting the importance of TB prevention. The bacilli Calmette-Guérin (BCG) vaccine that is currently available can protect younger children but is less effective in adults, the major source of TB transmission. In addition, the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains and the high prevalence of HIV infection have significantly complicated TB prognosis and treatment. Together, these data highlight the need for new and more effective vaccines. Recently, several vaccines containing multiple antigens, including some of those specific for dormant Mtb strains, have been developed. These vaccines appear to be the best approach for satisfactory Mtb prevention. However, until a new vaccine is proven more effective and safe than BCG, BCG should remain part of the immunization schedules for neonates and children at risk for TB as a fundamental prophylactic measure.

Adolescent vaccine co-administration and coverage in New York City: 2007-2013.

OBJECTIVES: To investigate adolescent vaccination in New York City, we assessed tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate (MCV4), and human papillomavirus (HPV) vaccine uptake, vaccine co-administration, and catch-up coverage over time. METHODS: We analyzed data from the Citywide Immunization Registry, a population-based immunization information system, to measure vaccine uptake and co-administration, defined as a Tdap vaccination visit where MCV4 or HPV vaccine was co-administered, among 11-year-olds. Catch-up vaccinations were evaluated through 2013 for adolescents born 1996 to 2000, by birth cohort. HPV vaccination among boys included data from 2010 to 2013. RESULTS: Adolescent vaccine administration was greatest during the back-to-school months of August to October and was highest for Tdap. Although MCV4 uptake improved over the study years, HPV vaccine uptake among girls stagnated; boys achieved similar uptake of HPV vaccine by 2012. By 2013, 65.4% had MCV4 co-administered with Tdap vaccine, whereas 28.4% of girls and 25.9% of boys had their first dose of HPV vaccine co-administered. By age 17, Tdap and MCV4 vaccination coverage increased to 97.5% and 92.8%, respectively, whereas ≥1-dose and 3-dose HPV vaccination coverage were, respectively, 77.5% and 53.1% for girls and 49.3% and 21.6% for boys. Age-specific vaccination coverage increased with each successive birth cohort (P < .001). CONCLUSIONS: From 2007 to 2013, there were greater improvements in Tdap and MCV4 vaccination than HPV vaccination, for which co-administration with Tdap vaccine and coverage through adolescence remained lower. Parent and provider outreach efforts should promote timely HPV vaccination for all adolescents and vaccine co-administration.

Parental Tdap boosters and infant pertussis: a case-control study.

BACKGROUND: Although recommended for almost a decade, evidence for field effectiveness of vaccinating close adult contacts of newborn infants against pertussis ("cocooning") is lacking. We evaluated the impact of a government-funded cocoon program during a pertussis epidemic in New South Wales, Australia. METHODS: We matched all New South Wales laboratory-confirmed pertussis cases aged <4 months with onset between April 1, 2009, to March 30, 2011 to controls from the state birth register by date of birth and area of residence. Parental vaccine receipt was by self-report, with a subset verified. Parents were considered "immunized" if vaccinated ≥4 weeks before case symptom onset. The effectiveness of parental immunization (versus neither vaccinated) was quantified as (1 - odds ratio) × 100%. RESULTS: Case households had fewer immunized mothers (22% vs 32%) or fathers (20% vs 31%) but were more likely to include additional and older children. After adjustment, when both parents met our definition of immunized, risk of pertussis at<4 months of age was reduced by 51% (95% confidence interval 10% to 73%). Maternal vaccination prepregnancy and an immunized father reduced the risk by 51% (95% confidence interval 0% to 76%). CONCLUSIONS: Timely parental pertussis boosters provided significant protection. Evidence of protection from maternal vaccination prepregnancy is biologically plausible, and more precise data on the magnitude and duration of this is important for future policy recommendations.

Tuberculosis vaccine development at a divide.

PURPOSE OF REVIEW: Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. RECENT FINDINGS: Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. SUMMARY: With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

[Old problems and new strategies in the fight against pertussis]. / Vecchi problemi e nuove strategie nella lotta contro la pertosse.

Pertussis is still a major Public Health problem. In fact, despite high vaccination coverage, several outbreaks have occurred in the last years all over the world, with thousands of cases and several deaths. Waning immunity seems to be the origin of this phenomenon, causing the shift of the peak incidence of the disease from school-age children, typical of the pre-vaccination era, to adolescents and adults. From these subjects the infection spreads to infants who have not yet been vaccinated or who have not completed the vaccination cycle. To reduce the incidence and the complications of pertussis in infants and immune compromised persons, booster doses are recommended and a "cocoon" vaccination strategy has been proposed.

Annual report: Surveillance of adverse events following immunisation in Australia, 2011.

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2011, and describes reporting trends over the 12-year period 2000 to 2011. There were 2,327 AEFI records for vaccines administered in 2011, a decrease of 40% from 3,894 in 2010. The decrease in 2011 was attributable to a decline in reporting following seasonal influenza (2,354 to 483) and pandemic H1N1 (pH1N1) influenza vaccines (514 to 2). However, reporting rates for some other vaccines were higher in 2011 compared with 2010. The 13-valent pneumococcal conjugate vaccine (13vPCV) replaced the 7-valent pneumococcal conjugate vaccine (7vPCV) and was suspected of involvement in 236 AEFI cases (48 per 100,000 doses). An increase in the number of reports following rotavirus (from 40 to 56 per 100,000 doses), and the hexavalent infant vaccine (from 27 to 40 per 100,000 doses), may have been due at least in part to co-administration with 13vPCV. Reports following DTPa-IPV also increased (from 94 to 139 per 100,000 doses), continuing a trend since 2009. AEFI reports following receipt of the 23-valent pneumococcal vaccine also increased markedly in those aged ≥65 years, from 155 to 288 records. In response to the increase in reports following 23vPPV, boosters are no longer recommended for those without medical risk factors. The most commonly reported reactions were injection site reactions, fever, allergic reactions and malaise. Only 7% of all the reported adverse events were categorised as serious, as per the database definitions, although some events classified as non-serious may have caused severe illness. Three deaths were temporally associated with vaccination; however, all were attributed to causes other than vaccination. The increase in 2011 was predominately due to reports of injection site reactions (49% increase in 2011). Increases in some instances may also be partly attributable to an increasing propensity to report AEFI.

Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine.

OBJECTIVE: The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in preterm infants were assessed in this study. METHODS: Three parallel groups of infants received 3-dose primary immunization with PHiD-CV at 2, 4, and 6 months of age and a booster dose at 16 to 18 months: preterm I (gestation period ≥ 27 and <31 weeks, N = 50); preterm II (≥31 and <37 weeks, N = 87); and term (≥37 weeks, N = 149). Solicited symptoms and adverse events were recorded. Immune responses to PHiD-CV and coadministered vaccine antigens were measured. RESULTS: The incidence of solicited general symptoms was similar across groups, and the frequency of grade 3 general symptoms was low. Incidences of redness and swelling were generally lower in preterm infants. PHiD-CV was immunogenic for each of the 10 vaccine pneumococcal serotypes (postprimary, ≥92.7% of infants reached enzyme-linked immunosorbent assay antibody concentrations ≥ 0.2 µg/mL and postbooster, ≥97.6%) and for protein D, with a trend for lower postprimary geometric mean antibody concentrations and opsonophagocytic activity (OPA) titers in preterm infants for some pneumococcal serotypes. Postbooster, ≥91.9% of subjects in each group had an OPA titer ≥ 8 for each of the vaccine serotypes. Pneumococcal antibody concentrations and OPA titers after priming and booster vaccination were comparable between the 2 preterm groups. CONCLUSIONS: PHiD-CV was well tolerated and immunogenic in preterm infants when given as a 3-dose primary vaccination, with robust enzyme-linked immunosorbent assay antibody and OPA booster responses in the second year of life.

Combined, reduced-antigen content tetanus, diphtheria, and acellular pertussis vaccine (Boostrix): a review of its use as a single-dose booster immunization in individuals aged 10-64 years in the US.

Boostrix is a three-pertussis component, combined, reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine administered as a single intramuscular dose in adolescents or adults aged 10-64 years. Large, well designed trials conducted in the US in adolescents aged 10-18 years and in adults aged 19-64 years showed that serum concentrations of anti-pertussis antibodies approximately 1 month after Boostrix administration were noninferior to those previously shown to have a protective effect in infants following a primary regimen of combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine. Protective serum concentrations of anti-diphtheria and anti-tetanus antibodies were achieved in essentially all (>or=99.9%) adolescents randomized to receive Boostrix or tetanus and diphtheria toxoids (Td) vaccine, and Boostrix was noninferior to Td vaccine for these endpoints. Similarly high seroprotection rates against diphtheria and tetanus were demonstrated with Boostrix and a five-pertussis component Tdap booster vaccine (Adacel) in a large, randomized study in adults; Boostrix was noninferior to Adacel for these outcomes. Reactogenicity data indicate that the vaccine is generally well tolerated in terms of solicited local and general symptoms in both adults and adolescents. Moreover, the importance of single-dose booster vaccination with a Tdap vaccine (such as Boostrix) in these populations is highlighted in current immunization guidelines. Therefore, as a single-dose booster vaccine, Boostrix provides a useful option to reduce pertussis morbidity and maintain the standard of care for tetanus and diphtheria protection in individuals aged 10-64 years.

Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer.

Prostvac is a prostate cancer vaccine regimen consisting of a recombinant vaccinia vector as a primary vaccination, followed by multiple booster vaccinations employing a recombinant fowlpox vector. Both vectors contain the transgenes for prostate-specific antigen (PSA) and multiple T-cell co-stimulatory molecules (TRICOM). The PSA-TRICOM vaccines infect antigen-presenting cells (APCs) and generate proteins that are expressed on the surface of the APCs in an immune context. The interaction of these APCs with T cells initiates a targeted immune response and T cell-mediated tumor cell destruction. Preliminary clinical trials have indicated negligible toxicity, and Phase II trials have suggested a survival benefit after treatment with Prostvac, especially in patients with indolent disease characteristics. Preclinical and clinical data indicate that radiation, hormonal therapy, and chemotherapy may be combined with Prostvac to enhance the vaccine's efficacy. Additional strategies are in development to further enhance the clinical benefits of Prostvac, and a Phase III trial is being planned in metastatic castration-resistant prostate cancer.

[Who is it necessary to vaccine against whooping-cough?]. / Qui faut-il vacciner contre la coqueluche?

Whooping-cough is one of the rare diseases for which vaccine prevention has been available for many years. However, in spite of good vaccine coverage in the infant, the pertussis infection remains a frequent disease in the teenagers and adults partially immunized. The missing diagnosis of the infection, added to its often clinical banal expression, contributes to support the circulation of Bordetella pertussis and explains the contamination of the young infants in whom the disease remains a true danger as the few declared deaths show it every year. Control of the disease must go through reinforcement of vaccination as a practitioner of booster vaccine in preadolescents, teenagers and adults. Instituted since 1998 in the French vaccine calendar, the 2nd booster in preadolescence between 11-13 years olds or 5th dose of vaccine is not enough carried out and must be encouraged like the installation of another additional vaccine dose for adults and certain professional categories. The protection of infants too young to have received the 3 doses goes through the vaccination of their entourage, family and socio-professional alike. The new recommendations thus preach to begin vaccination in children from the age of 2 months, a reinforcement of the vaccine boosters in preadolescents, in adults likely to become parents and in the medical and paramedical personnel in contact with very young infants.