Vaccine-naive Children Research Articles

The Potential Role of Patient Portals to Improve Influenza Vaccination.

* Abbreviation: COVID-19 — : coronavirus disease 2019 Each year, before 2020, millions of children contracted influenza virus.1 From 2020 to 2021, protective measures to prevent the spread of coronavirus disease 2019 (COVID-19), such as mask wearing, social distancing, and frequent hand-washing, likely protected children from other infectiousdiseases, including seasonal influenza.2 However, as COVID-19 preventive measures begin to abate and children return to school and normal activities outside the home, the seasonal influenza will again be a threat to young children nationally. Children under 18 years of age are twice as likely to develop symptoms as adults over age 65 years, and those under 4 years of age are over 3 times as likely.1 Young children, especially those under 5 years old, are at the highest risk for severe illness and death from influenza.1,3 Children are also key drivers of transmission, on average spreading influenza to multiple age groups and for longer periods than adults.4 Influenza vaccination is still the best method of preventing influenza and its associated complications. Influenza vaccine should be given to children starting at age 6 months, and 2 doses of influenza vaccine, administered 28 days apart, should be given to a child under age 9 years if they have not previously received 2 doses during an influenza season. Previous studies have shown the importance of both doses, especially in vaccine-naive children. For example, in vaccine-naive children aged 2 years or younger, vaccine effectiveness is cut … Address correspondence to Melissa S. Stockwell, MD, MPH, Division of Child and Adolescent Health, Department of Pediatrics, Vagelos College of Physicians & Surgeons, Columbia University, 622 W 168th St, VC 417, New York, NY 10032. E-mail: mss2112{at}cumc.columbia.edu

Mumps Antibody Titer in MMR-Vaccinated and Vaccine Naïve Children at a Public Hospital in Delhi

To compare the mumps antibody titers in Measles-Mumps-Rubella (MMR)-vaccinated and vaccine naive children. This cross-sectional study was conducted at a tertiary-care public hospital in Delhi from November, 2016 to April, 2018 among 78 healthy children (aged 16 month-12 years) attending the pediatric outpatient department. Serum IgG and IgM rubella antibodies were measured by ELISA for confirmation of MMR vaccination status. Qualitative determination of IgG mumps was done followed by quantitative determination in samples positive for IgG mumps antibodies. IgG mumps was present in 69.2% of study population, with seroprotective titers in 32% taking endpoint titer as 1:4. Among MMR vaccinated children, 41.1% were sero-protected and in MMR vaccine naïve children 9.1% were seroprotected for mumps. Single dose of MMR vaccine does not provide effective (>90%) sero-conversion required for successful herd immunity to prevent mumps outbreak.

Determination of ELISA reactive mumps IgG antibodies in MMR vaccine recipients in comparison with MMR vaccine naive children: A cross sectional study

Background/Aim: Mumps is by vaccine preventable infectious disease characterised by parotitis. In India mumps vaccines are not currently used under National Immunisation Programme (NIP). Waning of vaccine-induced immunity is considered to play a central role in the re-emergence of mumps. The comprehensive data on the seroepidemiology of measles, mumps, and rubella (MMR) as well as studies which compare the antibody titre among mumps vaccine naiveand mumps vaccinated children are lacking. The aim of this study was to estimate and compare mumps specific antibody titre in children with and without MMR vaccine. Methods: In 2019/2020, blood samples were collected from 100 healthy children attending immunisation clinic in Government Medical College Kota and associated J K Lon Maternal and Child care hospital Kota. The samples were investigated for MMR IgG antibodies using ELISA. Results: Out of total 100 children included in the study, 32.27 % vaccinated and 4.83 % non-vaccinated children were positive for mumps IgG antibody in the age group of 6 months to 6 years of age. Children aged 6 to 12 years, vaccinated and non-vaccinated, had 31.57 % and 26.57 % positivity, respectively. The seroprevalence of measles, mumps and rubella antibodies among 50 MMR vaccinated children were 94 %, 64 %, and 96 %, respectively. A high measles and rubella seroprevalences were observed among all children age groups, suggesting an effective control program, while the mumps seroprevalence decreased significantly with age. Conclusion: The maximum vaccine effectiveness against mumps for 2 doses of MMR vaccine is ≈ 96 %. The herd immunity threshold to block mumps virus transmission is ≥ 86 %. In this study only 64 % of the vaccinated children were found to have IgG mumps antibodies. In view of morbidity following mumps infection there is a need to incorporate mumps vaccine along with measles and rubella vaccine in the NIP instead of Mr.

Patterns of Influenza Vaccination and Vaccine Effectiveness Among Young US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness

The burden of influenza among young children is high, and influenza vaccination is the primary strategy to prevent the virus and its complications. Less is known about differences in clinical protection following 1 vs 2 doses of initial influenza vaccination. To describe patterns of influenza vaccination among young children who receive outpatient care for acute respiratory tract illness in the US and compare vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza by number of influenza vaccine doses received. This test-negative case-control study was conducted in outpatient clinics, including emergency departments, at 5 sites of the US Influenza Vaccine Effectiveness Network during the 2014-2015 through 2017-2018 influenza seasons. The present study was performed from November 5, 2014, to April 12, 2018, during periods of local influenza circulation. Children aged 6 months to 8 years with an acute respiratory tract illness with cough who presented for outpatient care within 7 days of illness onset were included. All children were tested using real-time, reverse-transcriptase polymerase chain reaction for influenza for research purposes. Vaccination in the enrollment season with either 1 or 2 doses of inactivated influenza vaccine as documented from electronic medical records, including state immunization information systems. Medically attended acute respiratory tract infection with real-time, reverse-transcriptase polymerase chain reaction testing for influenza. Of 7533 children, 3480 children (46%) were girls, 4687 children (62%) were non-Hispanic white, and 4871 children (65%) were younger than 5 years. A total of 3912 children (52%) were unvaccinated in the enrollment season, 2924 children (39%) were fully vaccinated, and 697 children (9%) were partially vaccinated. Adjusted VE against any influenza was 51% (95% CI, 44%-57%) among fully vaccinated children and 41% (95% CI, 25%-54%) among partially vaccinated children. Among 1519 vaccine-naive children aged 6 months to 2 years, the VE of 2 doses in the enrollment season was 53% (95% CI, 28%-70%), and the VE of 1 dose was 23% (95% CI, -11% to 47%); those who received 2 doses were less likely to test positive for influenza compared with children who received only 1 dose (adjusted odds ratio, 0.57; 95% CI, 0.35-0.93). Consistent with US influenza vaccine policy, receipt of the recommended number of doses resulted in higher VE than partial vaccination in 4 influenza seasons. Efforts to improve 2-dose coverage for previously unvaccinated children may reduce the burden of influenza in this population.

Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules.

One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children. Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children. Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4% (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100% (NZ98/254) and 90%-100% (M10713). We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12-24 months, and doses at 12-24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638.

Antibody concentrations against the infecting serotype in vaccinated and unvaccinated children with invasive pneumococcal disease in the United Kingdom, 2006-2013.

This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 µg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 µg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 µg/mL) vs other vaccine serotypes (15.64 µg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations <0.35 µg/mL against their infecting serotype generally remained unresponsive despite further vaccine doses. However, recurrent IPD with the same infecting serotype was rare (7/3030 children [0.2%]) and not associated with unresponsiveness. Vaccination with PCV before and/or after IPD was associated with lower IgG concentrations against the infecting serotype compared with other vaccine serotypes, but recurrent IPD was rare. Further studies are needed to understand this phenomenon in immunized children.

Live Attenuated Influenza Vaccine (FluMist®; Fluenz™)

Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged ≤71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenza caused by antigenically-matching viral strains in a multinational phase III trial in children aged 6-59 months. LAIV was also significantly more effective than TIV in decreasing the incidence of culture-confirmed influenza illness in two open-label studies (in children with recurrent respiratory tract illnesses aged 6-71 months and in children and adolescents with asthma aged 6-17 years). LAIV did not differ significantly from placebo in preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III trial. However, LAIV significantly reduced the incidence of febrile upper respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI-related work absenteeism and healthcare provider use. In another well designed trial in adults, LAIV significantly reduced the incidence of symptomatic, laboratory-confirmed influenza compared with placebo (but not intramuscular TIV). LAIV was generally well tolerated in most age groups, with the majority of adverse events being mild to moderate in severity, and runny nose/nasal congestion being the most common. In a large phase III trial, LAIV, compared with TIV, was associated with an increased incidence of medically significant wheezing in vaccine-naive children aged <24 months and an increased incidence of hospitalization in children aged 6-11 months; LAIV is not approved for use in children <24 months. LAIV was not always associated with high rates of seroconversion/seroresponse, particularly in older children and adults, or in subjects with detectable levels of haemagglutination-inhibiting antibodies at baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and strong cell-mediated immunity responses. Only one confirmed case of LAIV virus transmission to a placebo recipient (who did not become ill) occurred in a transmission study conducted in young children. The immunogenic response to LAIV in young healthy children was not affected by concomitant administration with other commonly administered childhood vaccines. In conclusion, intranasal LAIV seasonal influenza vaccine is effective and well tolerated in children, adolescents and adults. LAIV was more effective than TIV in children, although this advantage was not seen in adults. In the US, LAIV is indicated for the active immunization of healthy subjects aged 2-49 years against influenza disease caused by virus subtypes A and type B contained in the vaccine.

Efficacy of live attenuated influenza vaccine in children against influenza B viruses by lineage and antigenic similarity

Seasonal influenza vaccines, including live attenuated influenza vaccine (LAIV), contain three vaccine strains (two type A and one type B). Ideally, the hemagglutinin antigens of the recommended vaccine strains are antigenically similar to epidemic wild-type strains; in actuality, the antigenic match between circulating and vaccine strains each year can vary significantly owing to intermittent genetic reassortment and continuous antigenic drift. For influenza B, antigenic relatedness is further complicated by the existence of two distinct lineages. Consequently, the influenza B vaccine component can be of a completely different antigenic lineage from the circulating epidemic strains. Using data from nine randomized clinical trials in young children (6 months to 6 years of age), vaccine efficacy of LAIV against influenza B strains was assessed across this spectrum of antigenic relatedness. In an integrated analysis, vaccine efficacy of two doses of LAIV in vaccine-naive children was 86% against B strains of the same lineage and closely matched to the vaccine strain, 55% against strains of the same lineage but antigenically drifted from the vaccine strain, and 31% against strains of the opposite B lineage and antigenically unrelated to the vaccine strain. These data provide a more accurate assessment of the protection provided by the current trivalent vaccine and highlight the need for vaccination strategies that provide enhanced protection against both lineages of influenza B such as a quadrivalent influenza vaccine.

Efficacy and Safety of 1 and 2 Doses of Live Attenuated Influenza Vaccine in Vaccine-Naive Children

We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to <36 months. Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV. In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2. One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in children > or =2 years of age.

Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials

Nine randomized clinical trials, including approximately 25,000 children aged 6–71 months and 2000 children aged 6–17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza as compared to placebo or trivalent inactivated vaccine (TIV). We conducted meta-analyses, based on Mantel–Haenszel relative risks from fixed effect models, to provide an estimate of vaccine efficacy (VE). Relative to placebo, year 1 VE for two doses in vaccine-naïve young children was 77% (95% CI: 72%, 80%; P<0.001) against antigenically similar strains and 72% against strains regardless of antigenic similarity. Efficacy was 85%, 76%, and 73% against antigenically similar A/H1N1, A/H3N2, and B, respectively. Year 1 VE of one dose against antigenically similar strains in vaccine-naive children was 60%; efficacy of one dose in previously vaccinated children in year 2 of the various studies was 87%. In head-to-head trials comparing two doses of TIV and LAIV, vaccine-naïve children who received two doses of LAIV experienced 46% fewer cases of influenza illness caused by antigenically similar strains. Similarly, for studies including older children who had been previously vaccinated, those receiving one LAIV dose experienced 35% fewer cases of influenza illness than those receiving one TIV dose. LAIV showed high VE versus placebo with no evidence of difference by age or by circulating subtype. In these studies, LAIV was more effective than TIV.

Humoral and Cellular Response to Influenza Vaccine in HIV-Infected Children With Full Viroimmunologic Response to Antiretroviral Therapy

It is unclear whether the ability to respond to vaccines is restored by antiretroviral therapy. We evaluated the influenza-specific immune responses elicited by a virosomal vaccine in HIV-infected children on long-term successful highly active antiretroviral therapy (HAART). This was an observational, prospective, open-label study enrolling 24 HIV-infected, HAART-treated (85 months' mean exposure), vaccine-naive children (median age=11.9 years) and 14 age- and gender-matched healthy controls. Mean CD4 T-cell counts (>900 cells/microL) and percentages (>37%) were comparable. The HIV RNA level was <50 copies/mL in all patients. Children received a single dose of trivalent virosome-adjuvanted influenza vaccine. A/H3N2-, A/H1N1-, and B-antigen-specific antibody (Ab) titers and subclasses and vaccine-specific interferon-gamma (IFNgamma)- and interleukin (IL)-2-producing T lymphocytes were analyzed at baseline and 1 and 6 months after immunization. Seroconversion (>or=4-fold Ab titer raise in >40% of patients) and seroprotection (Ab titer>or=1:40 in >70% of patients) was achieved at 1 month in both groups; however, fewer HIV-infected children fulfilled these criteria. The A/H3N2- and A/H1N1-specific Ab geometric mean titers were lower in HIV-infected children compared with healthy controls at 1 and 6 months; interestingly, a boost in vaccine-specific IgG3 T helper 1 type Ab was seen in healthy controls alone. Finally, vaccine specific-IFNgamma- and IL-2-producing T lymphocytes were reduced at both time points in HIV-infected children compared with healthy controls. One injection of virosomal-adjuvanted influenza vaccine stimulates good immune responses, although the humoral and cellular immune responses are reduced in HIV-infected children compared to healthy children. This indicates that immunologic function impairments may persist upon HIV infection even if HIV-positive viremia is suppressed and immune recovery seems to be achieved.

Influenza Vaccine Immunogenicity in 6- to 23-Month-Old Children: Are Identical Antigens Necessary for Priming?

Influenza Vaccine Immunogenicity in 6- to 23-Month-Old Children: Are Identical Antigens Necessary for Priming?