Role of the National Immunisation Technical Advisory Groups in 13 European countries in the decision-making process on vaccine recommendations.

In Europe, National Immunisation Technical Advisory Groups (NITAGs) were established in most countries to promote evidence-informed decision-making in introducing new or improved vaccines or changing recommendations for existing ones. Still, the role, activities and outcomes of NITAGs have not been optimally implemented across Europe. Within the European Joint Action on Vaccination (EU-JAV), we conducted a survey to collect information on decision-making process including the main criteria for the introduction of new vaccines or changes to recommendations on their use. Between December 2021 and January 2022, 13 of the 28 European countries invited participated in an online survey. The criteria ranked as most relevant were disease burden and availability of financial resources. Only one country specified that the NITAG recommendations were binding for the government or the health authority. Vaccinations more often reported for introduction or recommendation changes were those against herpes zoster, influenza, human papillomavirus infection, pneumococcal and meningococcal disease. The planned changes will mainly address children and adolescents (2-18 years) and adults (≥ 45-65 years). Our findings show potential overlaps in the activities of NITAGs between countries; and therefore, collaboration between NITAGs may lead to optimisation of the workload and better use of resources.

Immunisation schedule of the Spanish Association of Paediatrics: 2023 Recommendations.

As it does every year, the CAV-AEP publishes the update of its recommendations for the use of vaccines in children, adolescents and pregnant women residing in Spain. The 2 + 1 schedule is maintained in infants (at 2, 4 and 11 months), including preterm infants, with the hexavalent vaccine (DTaP-IPV-Hib-HB) and the pneumococcal 13-valent conjugate vaccine. A booster dose with DTaP-IPV is needed at 6 years for those who received the 2 + 1 series with hexavalent vaccine as infants, in addition to 1 dose of dTap in adolescence. Routine vaccination of pregnant women with a dose of dTap is recommended in each pregnancy, preferably between weeks 27 and 32 of gestation, although can be given from 20 weeks if there is risk of preterm delivery. All infants should receive the rotavirus vaccine (2-3 doses) and the 4CMenB vaccine (2 + 1 series). All children aged 6-59 months should be vaccinated against influenza each year. The MenACWY vaccine should be given routinely at 12 months of age and in adolescence between ages 12 and 18 years. The recommendations for the MMR vaccine (12 months and 3-4 years) and varicella vaccine (15 months and 3-4 years) also remain unchanged, using the MMRV vaccine for the second dose. Recommendations for the use of SARS-CoV-2 vaccines in the paediatric age group will be updated periodically on the CAV-AEP website. The HPV vaccine is indicated in all adolescents, regardless of sex, at age 12 years. Novelties include the recommendation of routine administration of nirsevimab to neonates and infants aged less than 6 months for passive immunization against RSV, and the recommendations regarding the hexavalent vaccine are consolidated in a single section.

Immunization schedule of the Pediatric Spanish Association: 2022 recommendations.

After reviewing the best available scientific information, CAV-AEP publishes their new recommendations to protect pregnant women, children and adolescents living in Spain through vaccination. The same recommendations as the previous year regarding hexavalent vaccines, pneumococcal conjugate vaccine of 13 serotypes, booster with tetanus, diphtheria, pertussis and inactivated poliomyelitis (Tdpa-IPV) at 6 years and with tetanus, diphtheria and pertussis (Tdpa) at 12-14 years and pregnant women from week 27 (from week 20 if there is a high risk of preterm delivery). Also with rotavirus, tetraantigenic meningococcal B (2+1), meningococcal quadrivalent (MenACWY), MMR, varicella and human papillomavirus (HPV) vaccines, for both genders. As novelties this year the CAV-AEP recommends: Influenza vaccination from 6 to 59 months of age whenever feasible and does not harm the vaccination program aimed at people at higher risk. According to official national recommendations, the CAV-AEP recommends the systematic use of COVID mRNA vaccines since 5 years old.

Adherence to the paediatric immunisation schedule in England.

Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS's immunisation schedule and potential factors of schedule adherence. Immunisation data was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We collected vaccine types, doses, and dates for all routine paediatric vaccines between 2008 and 2018: DTaP/IPV/Hib/HepB, DTaP/IPV/Hib, DTaP/IPV, dTaP/IPV, Td/IPV, MMR, PCV, MenB, MenC, MenACWY, Hib/MenC, RV, HPV. Adherence to the immunisation schedule was calculated for each vaccine and dose. Differences in adherence between genders, NHS regions, and IMD quintiles were analysed. Our study included 6'257'828 vaccinations in 1'005'827 children. Seventy-five percent of first doses were administered within one (for vaccines scheduled in the first year of life) or two months (for vaccines scheduled later in life) following the recommended age, 19% too late and 6% too early. About half of the subsequent doses were given timely. The time between first and second doses was too short for 36% of vaccinations while 13% of second doses were administered too long after the first dose. Third doses were administered timely for 45%, too short for 37%, and too long for 18% of vaccinations. Differences in immunisation schedule adherence between girls and boys were negligible, except for HPV, and differences between the four main NHS regions were small. Overall, immunisation schedule adherence improved slightly with decreasing deprivation according to the Index of Multiple Deprivation. Efforts are required to improve the timeliness of paediatric vaccinations and to assure adequate protection against vaccine preventable diseases. We propose developing a compound measure combining coverage and adherence to provide a better indication of the protection against vaccine preventable diseases in a community.

Co-administration of routine paediatric vaccines in England often deviates from the immunisation schedule.

Vaccine co-administration can facilitate the introduction of new vaccines in immunisation schedules and improve coverage. We analysed real life data to quantify the extent of routine paediatric vaccine co-administrations as recommended and as never recommended in the immunisation schedule in England, and assessed factors for recommended and never recommended vaccine co-administrations. Immunisation data for all scheduled routine paediatric vaccines between 2008 and 2018 was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We included 6'257'828 doses administered to 1'005'827 children. Twenty-one percent of vaccines were given separately, 79% were co-administered. Sixty-four percent of vaccines scheduled for co-administration were co-administered as recommended while 15% were administered separately. Among all vaccine co-administrations, 75% happened as recommended in the schedule, 4% were never recommended, while 21% deviated from the schedule. Vaccine co-administration according to the schedule varied greatly between vaccines. Forty-eight percent of English children received at least one of their vaccine co-administrations not as recommended in the immunisation schedule, with 19% of children receiving none of their co-administered vaccines as recommended. Late administration of one or more vaccines increased the odds for deviated co-administrations (OR 1.60) and strongly increased the odds for never recommended co-administrations (OR 5.34). Differences between genders, NHS regions, and IMD quintiles were statistically significant but small. Suboptimal co-administration rates for routine paediatric vaccines are a missed opportunity and should be optimised by concerted public health action.

[Immunisation schedule of the Pediatric Spanish Association: 2021 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2021.

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children and adolescent resident in Spain, taking into account the available evidence. The 2+1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate.A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2+1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for triple viral (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, regardless of gender, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders.

[Immunisation schedule of the Spanish Association of Paediatrics: 2020 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2020.

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children resident in Spain, taking into account the available evidence. The 2+1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2+1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, both for girls and boys, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders.

[Immunisation schedule of the Spanish Association of Paediatrics: 2019 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2019.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. As regards funded immunisations, the 2+1 strategy (2, 4, 11 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, with a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy between 27 and 32 weeks gestation. The 2-dose scheme should be used for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years). MMRV vaccine could be applied as the second dose. Vaccination against HPV is recommended in both genders, preferably at 12 years of age. A stronger effort should be made to improve vaccination coverage. The new 9-valent vaccine is now available, expanding the coverage for both genders. Tetravalent meningococcal vaccine (MenACWY) is recommended at 12 months and 12-14 years, with a catch-up up at 19 years of age. It is also recommended in infants older than 6 weeks of age with risk factors, or travellers to countries with high incidence of ACWY meningococcal serogroups. As regards non-funded immunisations, it is recommended meningococcal B vaccination, with a 2+1 schedule, and requests that it be included in the National Immunisation Program. Vaccination against rotavirus is recommended in all infants.

[Immunisation schedule of the Spanish Association of Paediatrics: 2018 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría (CAV-AEP): recomendaciones 2018.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. Regarding funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, and a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy between 27 and 32 weeks' gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). MMRV vaccine could be applied as the second dose if available. Coverage of human papillomavirus vaccination in girls aged 12 with a two dose scheme (0, 6 months) should be improved. Information and recommendation for male adolescents about potential beneficial effects of this immunisation should be provided as well. The new 9 genotypes vaccine is now available, expanding the coverage for both gender. Regarding non-funded immunisations, Committee on Vaccines of the Spanish Association of Paediatrics recommends meningococcal B vaccination, with a 3+1 schedule, and requests to be included in the National Immunisation Program. Tetravalent meningococcal vaccine (MenACWY) is recommended to adolescents (14-18 years) who are going to live in countries with systematic vaccination against ACWY serogroups, and people >6 weeks of age with risk factors or travellers to countries with very high incidence. Vaccination against rotavirus is recommended in all infants.

[Immunisation schedule of the Spanish Association of Paediatrics: 2017 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría (CAV-AEP): recomendaciones 2017.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV- AEP) annually publishes the immunisation schedule which, in our opinion, is considered optimal for children resident in Spain, taking into account the evidence available on current vaccines. Pneumococcal and varicella immunisation in early childhood is already included in all funded vaccines present in the regional immunisation programmes. Furthermore, this committee establishes recommendations on vaccines not included in official calendars (non-funded immunisations), such as rotavirus, meningococcal B, and meningococcal ACWY. As regards funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTaP-IPV-Hib-HB) and 13-valent pneumococcal vaccines is recommended. Administration of the 6-year booster dose with DTaP is recommended, as well as a poliomyelitis dose for children who had received the 2+1 scheme, with the Tdap vaccine for adolescents and pregnant women between 27 and 32 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 12 with a two-dose scheme (0, 6 months) should be improved. Information and recommendations for male adolescents about potential beneficial effects of the tetravalent HPV vaccine should also be provided. ACWY meningococcal vaccine is the optimal choice in adolescents. For recommended unfunded immunisations, the CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish community pharmacies, with a 3+1 scheme. CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants.

An exploration of individual- and population-level impact of the 2-dose HPV vaccination schedule in pre-adolescent girls.

Since 2014, several countries have implemented a 2-dose schedule for Human papillomavirus (HPV) vaccination. Licensure of the 2-dose schedule was based on non-inferiority results from immunobridging studies, comparing the antibody levels of the 2-dose schedule in young girls to those of the 3-dose schedule in young adults. Since licensure, additional data on antibody levels and other aspects of the immune response and clinical effectiveness have become available. This review will discuss the current outcomes on immunogenicity and effectiveness together with an exploration on the population impact of 2-dose schedules from a cost-effectiveness perspective. The 2-dose schedule has important benefits, such as easier logistics, reduced expenditure, potentially higher acceptance and fewer side effects. Policymakers and registration authorities should consider whether these benefits outweigh the likely differences on individual- and population-level impact between the 2- and 3-dose schedules.

[Immunisation schedule of the Spanish Association of Paediatrics: 2016 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría (CAV-AEP): recomendaciones 2016.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) annually publishes the immunisation schedule which, in our opinion, estimates optimal for children resident in Spain, considering available evidence on current vaccines. We acknowledge the effort of the Ministry of Health during the last year in order to optimize the funded unified Spanish vaccination schedule, with the recent inclusion of pneumococcal and varicella vaccination in early infancy. Regarding the funded vaccines included in the official unified immunization schedule, taking into account available data, CAV-AEP recommends 2+1 strategy (2, 4 and 12 months) with hexavalent (DTPa-IPV-Hib-HB) vaccines and 13-valent pneumococcal conjugate vaccine. Administration of Tdap and poliomyelitis booster dose at the age of 6 is recommended, as well as Tdap vaccine for adolescents and pregnant women, between 27-36 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 11-12 with a two dose scheme (0, 6 months) should be improved. Information for male adolescents about potential beneficial effects of this immunisation should be provided as well. Regarding recommended unfunded immunisations, CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish communitary pharmacies, with a 3+1 scheme (3, 5, 7 and 13-15 months). CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Annual influenza immunisation and vaccination against hepatitis A are indicated in population groups considered at risk.

[Immunisation schedule of the Spanish Association of Paediatrics: 2015 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2015.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of current vaccines, including levels of recommendation. In our opinion, this is the optimal vaccination calendar for all children resident in Spain. Regarding the vaccines included in the official unified immunization schedule, the Committee emphasizes the administration of the first dose of hepatitis B either at birth or at 2 months of life; the recommendation of the first dose of MMR and varicella vaccine at the age of 12 months, with the second dose at the age of 2-3 years; DTaP or Tdap vaccine at the age of 6 years, followed by another Tdap booster dose at 11-12 years old; Tdap strategies for pregnant women and household contacts of the newborn, and immunization against human papillomavirus in girls aged 11-12 years old with a 2 dose scheme (0, 6 months). The Committee reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule, the same as it is being conducted in Western European countries. The recently authorised meningococcal B vaccine, currently blocked in Spain, exhibits the profile of a universal vaccine. The Committe insists on the need of having the vaccine available in communitary pharmacies. It has also proposed the free availability of varicella vaccines. Their efectiveness and safety have been confirmed when they are administred from the second year of life. Vaccination against rotavirus is recommended in all infants. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A.

[Immunisation schedule of the Spanish Association of Paediatrics: 2014 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2014.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the prevention of this disease. In anticipation of upcoming national and international studies, the Committee recommends the vaccine for the control of disease outbreaks, and insists on the need to be available in pharmacies. Finally, it emphasises the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule.