Humoral immunity against SARS-CoV-2 evoked by heterologous vaccination groups using the CoronaVac (Sinovac) and BNT162b2 (Pfizer/BioNTech) vaccines in Chile.

Introduction: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. Methods: We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. Results: We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. Discussion: These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.

Low Vaccine Coverage and Factors Associated with Incomplete Childhood Immunization in Racial/Ethnic Minorities and Rural Groups, Central Brazil.

Discrimination and limited access to healthcare services in remote areas can affect vaccination coverage. Therefore, this study aimed to estimate vaccination coverage for children living in quilombola communities and rural settlements in the central region of Brazil during their first year of life and to analyze the factors associated with incomplete vaccination. An analytical cross-sectional study was conducted on children born between 2015 and 2017. The percentage of children who received all vaccines recommended by the National Immunization Program in Brazil by 11 months and 29 days was used to calculate immunization coverage. Children who received the following vaccines were considered as having a complete basic vaccination schedule: one dose of BCG; three doses of Hepatitis B, of Diphtheria-Tetanus-Pertussis (DPT), of Haemophilus influenzae type b (Hib), and of Poliovirus (Polio); two doses of Rotavirus, of 10-valent pneumococcal (PCV10), and of Serogroup C meningococcal conjugate (MenC); and one dose of Yellow Fever (YF). Measles-mumps-rubella (MMR) and other doses recommended at or after 12 months were not included. Consolidated logistic regression was used to identify factors associated with incomplete vaccination coverage. Overall vaccination coverage was 52.8% (95% CI: 45.5-59.9%) and ranged from 70.4% for the Yellow Fever vaccine to 78.3% for the Rotavirus vaccine, with no significant differences between the quilombola and settler groups. Notably, the likelihood of incomplete general vaccination coverage was higher among children who did not receive a visit from a healthcare professional. Urgent strategies are required to achieve and ensure health equity for this unique and traditionally distinct group with low vaccination coverage.

Cost-effectiveness of various immunization schedules with inactivated Sabin strain polio vaccine in Hangzhou, China.

Background: It is necessary to select suitable inactivated poliovirus vaccine(IPV) and live, attenuated oral poliovirus vaccine (OPV) sequential immunization programs and configure the corresponding health resources. An economic evaluation was conducted on the sequential procedures of Sabin strain-based IPV (sIPV) and bivalent OPV (bOPV) with different doses to verify whether a cost-effectiveness target can be achieved. This study aimed to evaluate the cost-effectiveness of different sIPV immunization schedules, which would provide convincing evidence to further change the poliovirus vaccine (PV) immunization strategies in China. Methods: Five strategies were included in this analysis. Based on Strategy 0(S0), the incremental cost (IC), incremental effect (IE), and incremental cost-effectiveness ratio (ICER) of the four different strategies (S1/S2/S3/S4) were calculated based on the perspective of the society. Seven cost items were included in this study. Results of field investigations and expert consultations were used to calculate these costs. Results: The ICs of S1/S2/S3/S4 was Chinese Yuan (CNY) 30.77, 68.58, 103.82, and 219.82 million, respectively. The IE of vaccine-associated paralytic poliomyelitis (IEVAPP) cases of S1/S2/S3/S4 were 0.22, 0.22, 0.22, and 0.11, respectively, while the IE of disability-adjusted life-years (IEDALY) of S1/S2/S3/S4 were 8.98, 8.98, 8.98, and 4.49, respectively. The ICERVAPP of S1/S2/S3/S4 gradually increased to CNY 13.99, 31.17, 47.19, and 199.83 million/VAPP, respectively. The ICERDALY of S1/S2/S3/S4 also gradually increased to CNY 0.34, 0.76, 1.16, and 4.90 million/DALY, respectively. Conclusion: ICERVAPP and ICERDALY were substantially higher for S3 (four-sIPV) and S4 (replacement of self-funded sIPV based on one-sIPV-three-bOPV). Two-sIPV-two-bOPV had a cost-effectiveness advantage, whereas S2/S3/S4 had no cost-effectiveness advantage.

Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial.

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

Effects of SARS-CoV-2 on children treated at the first level of care in Buenos Aires city, 2019-2020 / Efectos de la pandemia por sars-cov-2 en niños asistidos en primer nivel de atención en la ciudad de buenos aires, 2019-2020

RESUMEN INTRODUCCIÓN: Debido a la pandemia por SARS-CoV-2 se registraron dificultades o interrupciones en los servicios sanitarios en diversos países, con el consiguiente riesgo para la salud de la población. En Argentina, existe evidencia de una disminución en el número de inmunizaciones aplicadas y la frecuencia de los controles periódicos de salud en pediatría. MÉTODOS: Se realizó un estudio descriptivo en tres centros de salud de la Ciudad de Buenos Aires. Se detallaron la cantidad de controles de salud y los esquemas de vacunación, entre otras variables, en niños nacidos en 2019 y 2020. RESULTADOS: Se revisaron 505 historias clínicas: 202 de 2019 y 303 de 2020. Los niños nacidos en 2019 y 2020 presentaron una mediana de 2 (rango intercuartílico [RI] 3) controles de salud por paciente entre los 0 y 6 meses. Entre los 7 y 12 meses, la mediana fue de 2 (RI 2) en 2019, y en 2020 fue 1 (RI 2). El esquema de vacunación a los 6 meses se encontraba completo en 32,68% (66) de los niños nacidos en 2019 y 34,65% (105) de los nacidos en 2020. DISCUSIÓN: La disminución en el número de controles de salud entre 7 y 12 meses, en los estudios de pesquisa y en las serologías maternas realizadas podría atribuirse al cambio de conductas sociales debido a la posibilidad de contagio o dificultades en la circulación de las personas al inicio de la pandemia. A diferencia de otras investigaciones, no se registró una disminución en la cobertura de vacunación en la población estudiada.

ABSTRACT INTRODUCTION: Due to the SARS-CoV-2 pandemic, difficulties and/or interruptions in health services were reported in various countries, with the consequent risk to the health of the population. In Argentina, there is evidence of a decrease in vaccination coverage and the frequency of pediatric check-ups. METHODS: A descriptive study was carried out in three health centers in the city of Buenos Aires. The number of health check-ups and vaccination schedules, among other variables, were detailed in children born in 2019 and 2020. RESULTS: A total of 505 medical records were reviewed: 202 from 2019 and 303 from 2020. Children born in 2019 and 2020 presented a median of 2 (interquartile range [IQR] 3) health check-ups per patient between 0 and 6 months. Between 7 and 12 months, the median was 2 (IQR 2) in 2019, and in 2020 it was 1 (IQR 2). The 6-month vaccination schedule was complete in 32.68% (66) of the children born in 2019 and 34.65% (105) of those born in 2020. DISCUSSION: The decrease in the number of health check-ups between 7 and 12 months, in the screening studies and in the maternal serologies performed could be attributed to the change in social behavior due to the possibility of contagion and/or difficulties in the movement of people at the beginning of the pandemic. Unlike other studies, a decrease in vaccination coverage was not found in the population studied.

Análisis económico de las vacunas del primer año de vida con componente pertussis en el contexto de la ini-ciativa mundial de erradicación de la poliomielitis en Argentina / Vaccination in children under 1 year with pertussis component in the context of the global initiative for the eradication of poliomyelitis in Argentina: economic analysis

INTRODUCCIÓN: La Iniciativa Mundial de Erradicación de la Polio promueve la introducción de vacuna de polio inactivada (IPV) en sus programas, con la posterior retirada de Sabin (bOPV). OBJETIVO: Construir un modelo de económico que compare diferentes esquemas de vacunación para la prevención de polio y tosferina en el primer año de vida. Material y MÉTODOS: Análisis de cuatro escenarios de vacunación del esquema primario para Argentina, en base a los precios de las vacunas, costos del programa y reactogenicidad de vacuna celular o acelular para Bordetella pertussis: - Escenario 1 (caso base): dos dosis de IPV, una dosis de bOPV y tres dosis de vacuna pentavalente (DTwP-HB-Hib); - Escenario 2: tres dosis IPV y de pentavalente; - Escenario 3: tres dosis de hexavalente (DTaP-HepB-IPV-Hib); - Escenario 4: dos dosis de hexavalente más una dosis de pentavalente más IPV. RESULTADOS: El costo incremental en base al escenario 1 fue de USD 3.716.671; 19.696.668 y 14.383.341 para los escenarios 2, 3 y 4, respectivamente. Para la reactogenicidad, la diferencia fue de USD -14.178.240 comparado el caso base con el escenario 3. DISCUSIÓN: La inversión de incorporación de full IPV y costos asociados se modifica según tipo de vacuna y reactogenicidad asociada al componente B. pertussis.

BACKGROUND: Global Polio Eradication Initiative promotes the introduction of inactivated polio vaccine (IPV) in its programs, with withdrawal of Sabin (bOPV). There is no an economic analysis of the investment related to the incorporation of IPV vaccines together with a whole cell Bordetella pertussis vaccine or combined with acellular hexavalent. AIM: An economic model that compares different vaccination schemes for the prevention of polio and pertussis in the first year of life was carried out. METHODS: Four vaccination scenarios for the primary scheme based on Argentina demographic and costs data were developed: - Scenario 1 (base case): two doses of IPV, one dose of bOPV and three doses of pentavalent (DTwP-HepB-Hib) vaccine; - Scenario 2: three doses of IPV plus three doses of pentavalent; - Scenario 3: three doses of hexavalent; - Scenario 4: two doses of hexavalent plus one dose of pentavalent plus IPV. RESULTS: The incremental cost based on scenario 1 was USD 3.716.671; 19.696.668 and 14.383.341 for scenarios 2, 3 and 4 respectively. In terms of reactogenicity savings was -14.178.240 compared base case with scenario 3. DISCUSSION: Full IPV introduction investment and costs associated were modified according to the type of vaccine and reactogenicity related with the B. pertussis component.

Immunogenicity and Reactogenicity of 13-Valent Pneumococcal Conjugate Vaccine Among Infants, Toddlers, and Children in Western Burkina Faso: Results From a Clinical Trial of Alternative Immunization Schedules.

BACKGROUND: Many African countries have introduced pneumococcal conjugate vaccine (PCV) into their routine immunization program to reduce the burden of morbidity and death that results from Streptococcus pneumoniae infection, yet immunogenicity and reactogenicity data from the region are limited for the 2 available PCV products. METHODS: We conducted a randomized trial of 13-valent PCV (PCV13) in Bobo-Dioulasso, Burkina Faso. Infants received 3 doses of PCV at 6, 10, and 14 weeks of age or at 6 weeks, 14 weeks, and 9 months of age; toddlers received 2 doses 2 months apart or 1 dose beginning at 12 to 15 months of age; and children received 1 dose between 2 and 4 years of age. We measured each participant's serotype-specific serum immunoglobulin G concentration and opsonophagocytic activity before and after vaccination. For each age group, we compared immune responses between study arms and between the standard schedule in our study and the PCV13-licensing trials. RESULTS: In total, 280 infants, 302 toddlers, and 81 children were assigned randomly and underwent vaccination; 268, 235, and 77 of them completed follow-up, respectively. PCV13 resulted in low reactogenicity in all the study arms. The vaccine elicited a strong primary immune response in infants after 2 or more doses and in children aged 1 to 4 years after 1 dose. Infants who received a booster dose exhibited a robust memory response. Immunogenicity was higher than or comparable to that observed in the PCV13-licensing trials for a majority of serotypes in all 3 age groups. CONCLUSIONS: PCV13 has a satisfactory immunogenicity and reactogenicity profile in this population. Our findings will help support decision making by countries regarding their infant and catch-up vaccination schedules.

Prolonged intervals during Mycobacterium tuberculosis subunit vaccine boosting contributes to eliciting immunity mediated by central memory-like T cells.

It is believed that central memory T cells (TCM) provide long-term protection against tuberculosis (TB). However, the effects of TB subunit vaccine immunization schedule, especially the vaccination intervals, on T cell immune memory is still unclear. In this study, mice were immunized with fusion protein ESAT6-Ag85B-MPT64 (190-198)-Mtb8.4-Rv2626c (LT70) based subunit vaccine three times according to the following schedules: ① 0, 3rd and 6th week respectively (0-3-6w), ② 0, 4th and 12th week (0-4-12w), and ③ 0, 4th and 24th week (0-4-24w). We found that both schedules of 0-4-12w and 0-4-24w induced higher level of antigen specific IL-2, IFN-γ and TNF-α than 0-3-6w immunization. Among them, 0-4-12w induced the highest level of IL-2, which is a key cytokine mainly produced by TCM. Moreover, by cultured IFN-γ ELISPOT and cell proliferation assay etc., we found that the vaccination schedule of 0-4-12w elicited higher numbers of TCM like cells, stronger TCM - mediated immune responses and higher protective efficacy against M. bovis BCG challenge than 0-3-6w did. It suggests that prolonging the vaccination interval of TB subunit vaccine to some extent contributes to inducing more abundant TCM like cells and providing stronger immune protection against mycobacteria infection.

Systematic literature review comparing rapid 3-dose administration of the GSK tick-borne encephalitis vaccine with other primary immunization schedules.

INTRODUCTION: Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.

Undervaccination with diphtheria, tetanus, and pertussis vaccine: National trends and association with pertussis risk in young children.

BACKGROUND: The high coverage for ≥3 pertussis vaccine doses among Taiwanese children might not imply timely vaccination. Recently, resurgence of pertussis and challenges with availability of DTaP-IPV-Hib prompted this study. METHODS: In the 1996-2012 national birth cohort, we calculated the prevalence and days of undervaccination against pertussis by age 36 months. We also compared the odds of undervaccination in each laboratory-confirmed pertussis patient at ages 3-35 months with sex-, residence-, and age-matched controls from the general population, using conditional logistic regression. RESULTS: The prevalence of undervaccination was 60.6% (median 16 days) and decreasing (p < 0.0001). Among 145 cases and 2,900 controls, 58 (40.0%) and 721 (24.9%) were undervaccinated (OR 2.28, 95% CI 1.57-3.31). The attributable risk percent was 22.5% (95% CI 14.5-27.9). CONCLUSIONS: Undervaccination was decreasing. Approximately up to one-fifth pertussis cases in children aged 3-35 months could have been prevented with on-time vaccination.

A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants.

BACKGROUND: The recommended schedule for receipt of 2-dose human rotavirus vaccine (HRV) coincides with receipt of the first and second doses of diphtheria, pertussis, and tetanus vaccine (ie, 6 and 10 weeks of age, respectively). Alternative schedules and additional doses of HRV have been proposed and may improve vaccine performance in low-income countries. METHODS: In this randomized trial in rural Ghana, HRV was administered at ages 6 and 10 weeks (group 1), 10 and 14 weeks (group 2), or 6, 10, and 14 weeks (group 3). We compared serum antirotavirus immunoglobulin A (IgA) seroconversion (≥20 U/mL) and geometric mean concentrations (GMCs) between group 1 and groups 2 and 3. RESULTS: Ninety-three percent of participants (424 of 456) completed the study per protocol. In groups 1, 2, and 3, the IgA seroconversion frequencies among participants with IgA levels of <20 U/mL at baseline were 28.9%, 37.4%, and 43.4%, respectively (group 1 vs group 3, P = .014; group 1 vs group 2, P = .163). Postvaccination IgA GMCs were 22.1 U/mL, 26.5 U/mL, and 32.6 U/mL in groups 1, 2, and 3, respectively (group 1 vs group 3, P = .038; group 1 vs group 2, P = .304). CONCLUSIONS: A third dose of HRV resulted in increased seroconversion frequencies and GMCs, compared with 2 doses administered at 6 and 10 weeks of age. Since there is no correlate of protection, a postmarketing effectiveness study is required to determine whether the improvement in immune response translates into a public health benefit in low-income countries. CLINICAL TRIALS REGISTRATION: NCT015751.

Meningococcal serogroup B vaccine in Italy: state-of-art, organizational aspects and perspectives.

Neisseria meningitidis causes severe invasive meningococcal diseases (IMDs) in humans including meningitis and septicemia, responsible for serious clinical conditions and leading to life-long disabilities and death. Serogroup B dominates IMDs burden in Italy, accounting for over 60% of total cases. On January 2013 the European Medicine Agency (EMA) licensed the first serogroup B meningococcal (MenB) vaccine in Europe. A number of European countries and Regions have introduced the new MenB vaccine in their immunization schedule, including Italy. In this paper we present the state of art, related critical issues and future perspectives of MenB vaccine introduction in Italy, in the context of the most recent available epidemiological data. In particular, we systematically assess the ongoing processes in the 8 Italian regions and one autonomous province that have already introduced MenB vaccine. With the new 2014-2018 National Vaccine Prevention Plan including active MenB vaccine offer about to be adopted, it is of fundamental importance to gather further evidence on MenB vaccine clinical effectiveness, duration of protection and cost-effectiveness. Italian regions are called to organize and manage MenB immunization programs. Careful consideration will need to be devoted on timing, doses, and co-administration with other vaccines but also to economic assessments and strengthened communication to the general public. Our data will help to plan, implement and evaluate MenB immunization programmes in other Italian and international settings.

Use of alternative childhood immunization schedules in King County, Washington, USA.

OBJECTIVE: To determine the percentage of parents in King County, Washington using an alternative childhood immunization schedule (ACIS) and the type of ACIS used. PATIENT AND METHODS: We distributed self-administered surveys to parents at 5 practices regarding the immunization schedule they planned to use or were using. Parents who selected an ACIS were asked to describe its main characteristics and information source. RESULTS: We received 517 surveys and included 502 in analysis. The percentage of parents using an ACIS was 9.4% (95% CI: 7%, 12.2%). Only 6% described their ACIS as the Dr. Sears Schedule, although the book in which it is featured was the most frequently cited ACIS information source (29%). There was a significant association between ACIS use and non-Hispanic white parents and parents of children 12-23 months old. CONCLUSION(S): A minority of King County parents use an ACIS. The Dr. Sears Schedule does not predominate.