Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza vaccine in children with juvenile idiopathic arthritis

In order to evaluate the immunogenicity, safety, and tolerability of the MF-59 adjuvanted seasonal influenza vaccine in children and adolescents with juvenile idiopathic arthritis (JIA) treated with different anti-rheumatic drugs, 60 pediatric patients with JIA (30 treated with disease-modifying anti-rheumatic drugs [DMARDs] and 30 with etanercept) were compared with 30 healthy controls of similar gender and age. All of the patients received a single dose of the MF59-adjuvanted seasonal influenza vaccine (Fluad, Siena, Italy). Immunogenicity was assessed at baseline, and 1 and 3 months post-vaccination; safety and tolerability were also evaluated during the study period. The JIA patients treated with etanercept showed significantly lower geometric mean titres (GMTs) against the A/H1N1 strain than those treated with DMARDs (p < 0.05) and the healthy controls (p < 0.05), who had similar GMTs. The etanercept-treated JIA patients also showed a significant reduction in GMTs against the A/H1N1 and A/H3N2 strains from 1 to 3 months after vaccination (p < 0.05). Furthermore, their seroconversion and seroprotection rates, and B antigen GMTs, were all significantly lower than those of the subjects in the other two groups (p < 0.05). The safety and tolerability of the vaccine were good and similar between the groups. The results of this study indicate a reduced immune response to MF59-adjuvanted seasonal influenza vaccine in JIA children and adolescents treated with etanercept in comparison with those treated with DMARDs and healthy controls. The safety and tolerability of the vaccine appeared to be good in all of the study population.     

A comparative study of the serological response to Japanese encephalitis vaccine in HIV-infected and uninfected Thai children

We report a prospective study of mouse brain derived inactivated Japanese encephalitis (JE) vaccine, given in 3-dose EPI program to human immune deficiency virus (HIV)-exposed Thai infants. 18 HIV-infected receiving antiretroviral therapy with median baseline CD4 of 33.1%, and 92 HIV-uninfected children were studied. All but one HIV-infected child seroconverted after the second dose. The geometric mean titers (GMTs) 3 months after the second and third doses in HIV-infected vs HIV-uninfected children were 247 vs 938 (p = 0.022), and 2273 vs 24069 (p = 0.009), respectively. Urticaria or angioedema found in 4% and 6% in HIV-infected and -uninfected children, respectively (p = 1.0). The vaccine was safe and immunogenic but antibody response in HIV-infected children was not as high as in uninfected children.     

Immunogenicity and safety of intradermal influenza vaccine in children

In order to compare the immunogenicity and safety of different doses of trivalent influenza vaccine (TIV) administered intradermallly (ID) with those evoked by a full dose of intramuscular (IM) virosomal-adjuvanted influenza vaccine (VA-TIV), 112 previously primed healthy children aged ≥3 years were randomised to receive 9 μg or 15 μg of each strain of ID-TIV, or a full IM dose (15 μg of each strain) of VA-TIV. The A/H1N1 and A/H3N2 seroconversion and seroprotection rates were ≥90% and geometric mean titres (GMTs) increased 3.2-14.9 times without any statistically significant between-group differences; however, the seroconversion and seroprotection rates against the B strain were significantly higher in the children receiving either ID-TIV dose (p < 0.05) without any differences between them. GMT against B virus was significantly higher in the children receiving the highest dose (p < 0.05). Local reactions were significantly more common among the children receiving either ID-TIV dose (p < 0.05), but systemic reactions were relatively uncommon in all three groups. Our findings suggest that ID-TIV with 15 μg of each viral antigen can confer a significant better protection against influenza than that obtained with the same dose of IM TIV in already primed children aged ≥3 years with an acceptable safety profile. The lower dose of ID-TIV needs further evaluation to analyze persistence of protection.     

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

Background and aims

We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD).

Methods

82 children (age 2–59 months) with sickle cell anemia (n = 22), chronic heart disease (n = 19), HIV infection (n = 12), immune-suppressive therapy (n = 11) and other IPD-predisposing conditions (n = 18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule.

Results

Pneumococcal carriage prior to the first immunization was 27% (n = 22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n = 17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p < 0.05).

Conclusions

PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children.     

Immunogenicity and safety of measles-mumps-rubella-varicella (MMRV) vaccine followed by one dose of varicella vaccine in children aged 15 months–2 years or 2–6 years primed with measles-mumps-rubella (MMR) vaccine

In this open, randomized, comparative study (105908/NCT00353288), 458 age-stratified children (15 months–2 years and 2–6 years) previously primed with MMR received one dose of either a combined MMRV vaccine (Priorix-Tetra™, MMRV group) or concomitant MMR and varicella vaccines (Priorix™ and Varilrix™, MMR + V group), followed 42–56 days later by another dose of varicella vaccine (Varilrix™) in both groups. Post-vaccination measles, mumps and rubella seropositivity rates and antibody geometric mean titers (GMTs) were high (99.5% for anti-measles and 100% for anti-mumps and anti-rubella) in both vaccine groups. In the two age strata, varicella seroconversion rates were, post-dose 1: ≥97.6% (MMRV), ≥96.6% (MMR + V) and, post-dose 2: 100% in both groups. Post-dose 2, anti-varicella GMTs increased respectively 14.1- and 12.6-fold (MMRV), and 9.8- and 13.1-fold (MMR + V). Both vaccine regimens were well-tolerated. Post-dose 1, the incidence of any solicited local symptom during the 4-days follow-up was ≤28.2% (MMRV) and ≤19.8% (MMR + V) and the incidence of fever >39.5 °C (rectal temperature) within 15 days was ≤2.8% (MMRV) and ≤2.6% (MMR + V). This MMRV vaccine appears an immunogenic and safe substitute for a second dose of MMR vaccine in young children. The increase in anti-varicella antibodies observed after a second dose of varicella vaccine supports a two-dose schedule for varicella-containing vaccine.     

Serum antibody response to three non-typeable Haemophilus influenzae outer membrane proteins during acute otitis media and nasopharyngeal colonization in otitis prone and non-otitis prone children

Non-typeable Haemophilus influenzae (NTHi) is the most common bacteria responsible for episodic acute otitis media (AOM; non-otitis prone), recurrent AOM (rAOM; otitis prone) and AOM treatment failure (AOMTF) in children. In this 3.5 years of prospective study, we measured the serum antibody response to outer membrane proteins D, P6 and OMP26 of NTHi in children with AOM (n = 26), rAOM (n = 32), AOMTF (n = 27). The geometric mean titers (GMTs) of IgG at their acute AOM visit against Protein D in otitis prone children were significantly lower compared to AOMTF (p value < 0.01) and non-otitis prone (p value < 0.03) children; otitis prone children had significantly lower IgG levels to P6 compared to AOMTF children (p value < 0.02); otitis prone children had significantly lower IgG levels to OMP26 compared to AOMTF children (p value < 0.04). Comparing acute to convalescent titers after AOM, otitis prone and AOMTF children had no significant change in total IgG against all the three proteins, while non-otitis prone children had significant increases to Protein D. Anti-protein D, P6 and OMP26 antibody levels measured longitudinally during NP colonization between age 6 and 24 months in 10 otitis prone children and 150 non-otitis prone children showed <2-fold increases over time in otitis prone children compared to >4 fold increases in the non-otitis prone children (p value < 0.001). We conclude that otitis prone children mount less of an IgG serum antibody response toward Protein D, P6 and OMP26 after AOM which may account for recurrent infections. The data on acute sera of otitis prone vs non-otitis prone children and the acute-to-convalescence response in non-otitis prone children point to a possible link of anti-PD to protection. Moreover, the data suggest that otitis prone children should be evaluated for their responses to Protein D, P6 and OMP26 vaccine antigens of NTHi.     

Immunogenicity and safety of influenza A (H1N1) 2009 monovalent inactivated split vaccine in Korea

In a pandemic, the development of an effective influenza vaccine is the most important subject from the view of public health. This study was performed to evaluate the immunogenicity and safety of inactivated, monovalent H1N1 2009 vaccine (Green Cross Corporation, Yongin, Korea) among healthy adults aged 19-64 years (Group 1) and the elderly aged ≥65 years (Group 2) in a two-dose regimen, 21 days apart. At baseline, 28 of 454 participants (6.1%) had hemagglutination-inhibition titers of ≥1:40 with no significant difference between age groups (p = 0.27). There was an apparent dose-dependent antibody response; participants receiving the dose of 30 μg hemagglutinin (HA) showed higher geometric mean titers (GMTs) than the 15 μg HA group in both age groups. Despite the rates of seroprotection and seroconversion were significantly higher with 30 μg HA formulation than 15 μg HA formula in Group 2, there was no definite difference in Group 1 irrespective of vaccine formula. Significant GMT elevation after the second dose was not noted in either age group, regardless vaccine formulations. No deaths, vaccine-related serious adverse events, or immediate unsolicited adverse reactions occurred during the study periods.     

Seroprevalence of anti-polio antibodies in a population 7 months to 39 years of age in Uruguay: Implications for future polio vaccination strategies

This study evaluated the seroprevalence of poliovirus types 1, 2 and 3 antibodies and vaccination coverage in 780 subjects aged between 7 months and 39 years in Montevideo, Uruguay, where oral polio vaccine (OPV) is used. Antibody titers were measured and seroprotection rates and geometric mean titers (GMTs) were compared among four age groups. Vaccination histories were recorded from documents and interviews. Seroprotection rates ranged from 72% to 95% in children aged 7–23 months, 31–77% in 2–9-year olds, 14–45% in 10–19-year olds and 20–59.5% in 20–39-year olds. Seroprotection decreased significantly with increasing age (p < 0.05). Polio vaccination coverage was >90% for the two youngest age groups. These results could help guide public policy decisions regarding polio vaccination, and support the use of inactivated polio vaccine following cessation of OPV.     

Immunogenicity and safety of a Haemophilus influenzae B (Hib)-hepatitis B vaccine with a modified process hepatitis B component administered with concomitant pneumococcal conjugate vaccine to infants

Background

A hepatitis B vaccine was manufactured with a modified process (mpHBV) that incorporated double the usual amount of phosphate. Following a study in young adults, the mpHBV was evaluated in infants in a combination hepatitis B and Haemophilus influenzae B vaccine (mpHBV-Hib).

Methods

The mpHBV-Hib was compared with the licensed bivalent HBV-Hib vaccine Comvax™ for immunogenicity and safety. Both vaccines contained 5 μg/0.5 mL of hepatitis B surface antigen (HBsAg) and 7.5 μg/0.5 mL of PRP-OMPC (polyribosylribitol phosphate outer membrane protein complex). A total of 543 infants were randomized 1:1 to receive either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose 3.

Results

Seroprotection rates [% subjects with anti-hepatitis B surface antigen antibody titers (anti-HBs) ≥10 mIU/mL)] were 100% and 99% for mpHBV-Hib and the licensed control (Comvax™), respectively. Anti-HBs geometric mean titers (GMTs) were 4204 (95% CI, 3411-5182) and 1683 (95% CI, 1350-2099) mIU/mL, respectively. Anti-PRP seroprotection rates (SPR) at ≥0.15 μg/mL and at ≥1.0 μg/mL were 97% and 94%, respectively, for mpHBV-Hib and 96% and 92%, respectively, for the control. Anti-PRP GMTs were 7.1 μg/mL for mpHBV-Hib and 8.0 μg/mL for the control. Reactogenicity of the two vaccines was similar.

Conclusions

The mpHBV in combination with Hib and with co-administered PCV was highly immunogenic. The safety profile of mpHBV-Hib was comparable to the licensed control. Both the control and mpHBV-Hib met acceptability criteria for seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV-Hib.     

The humoral immune response of hematopoietic stem cell transplantation recipients to AS03-adjuvanted A/California/7/2009 (H1N1)v-like virus vaccine during the 2009 pandemic

We evaluated the formation of hemagglutination-inhibition (HI) antibodies in response to vaccination of 55 allogeneic and 23 autologous hematopoietic stem cell transplantation (HSCT) recipients with 3.75 μg inactivated influenza A/California/7/2009 (H1N1)v-like virus adjuvanted with AS03, given towards the end of the 2009 influenza pandemic. The 78 HSCT recipients, aged 11-72 (median 50) years, were vaccinated 1-290 (median 27) months post-HSCT. Of the 55 allogeneic HSCT recipients, 50.9% received reduced intensity conditioning, 74.5% had a sibling donor, 67.2% had active graft-versus-host disease and 43.6% were on steroid therapy. At baseline, 14/78 (17.9%) had HI titers ≥1:40. Blood samples of 77 patients were available post-1st vaccination; of these, 34 (44.2%) patients had HI titers ≥1:40. Blood samples of 43 patients were available post-2nd vaccination; of these, 21 (48.8%) had HI titers ≥1:40. There was a significant increase in HI titers ≥1:40 from baseline to both post-1st and 2nd vaccinations (p < 0.001 each), and also from 1st to 2nd vaccination (p = 0.008). In seronegative (HI titers <1:10) patients, whose sera were available before, after one dose, and after 2 doses of vaccine, seroconversion (to ≥1:40) occurred in 4/24 (16.7%) after 1-dose and in a total of 10/24 (41.7%) after 2-dose vaccination (p = 0.031). Logistic regression analysis revealed that ≥1:40 HI titers were significantly associated with higher lymphocyte counts and higher HI baseline titers and, in allogeneic HSCT, with having a sibling donor and higher baseline titers. In conclusion, 2-dose vaccination with AS03-adjuvanted vaccine containing 3.75 μg antigen resulted in a statistically significant, yet limited, serological response. Therefore, additional precautions should be taken during influenza outbreaks.     

Randomized study of intradermal compared to intramuscular hepatitis B vaccination in HIV-infected children without severe immunosuppression

HIV infected individuals have poorer response to hepatitis B vaccine (HBV) compared to normal host. Intradermal administration (ID) facilitates the exposure of antigen to antigen-presenting cells compared to intramuscular administration (IM).HIV-infected children aged 1-18 years with CD4% ≥ 15% or 200 cells/mm³ who had negative HBs Ag, antiHBs, and antiHBc were randomized to receive 3-dose of HBV via ID (2 μg/dose) or IM (10 μg/dose) route at months 0, 2, and 6. AntiHBs titers were measured at months 2, 6 and 7 after first HBV. AntiHBs ≥ 10 mIU/mL was considered protective and AntiHBs > 100 mIU/mL was considered good response.Participants included 41 in ID and 39 in IM arms. 64% had completed 3-doses HBV during infancy. The mean (SD) of age, nadir CD4% and current CD4% were 12 (3.3) years, 10.6 (7.9)% and 28 (8.0)% respectively. 91% were on HAART and 84% had undetectable HIV-RNA.Proportion of children with protective antiHBs in ID vs. IM group were 19.5% vs. 25.6% at month 2, 56.1% vs. 76.9% at month 6, and 90.2% vs. 92.3% at month 7 (NS, all). The geometric mean (95% confidence interval) of antiHBs titer in ID vs. IM group were 112.5 (34.4-367.6) vs. 141.2 (49.4-404.1) mIU/mL at month 2 (p = 0.74), 70.4 (39.8-124.4) vs. 132.1 (79.4-219.8) mIU/mL at month 6 (p = 0.10), and 157.0 (103.0-239.3) vs. 458.9 (324.0-647.0) mIU/mL at month 7 (p < 0.001). However, only 56.1% of the ID arm had good response to HBV compared to 82.1% in the IM arm (p = 0.01). The predictors for being a good responder to HBV were IM administration [OR 4.0, 95%CI 1.4-11.8, p = 0.012] and body weight <35 kg at baseline [OR 3.8, 95%CI 1.3-10.8, p = 0.013]. No adverse events grade 3/4 occurred.In conclusion, HIV-infected children without severe immune suppression, both ID and IM routes of HBV resulted in similar rates of protective antibody titers. However, high antibody titers to HBV were more common with IM; therefore, IM administration is preferred.     

Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia

Background

In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction.

Methods

Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005–2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed.

Results

Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p = 0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p < 0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15 C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p < 0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p = 0.02).

Conclusions

A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.     

Anthrax vaccine adsorbed: Further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed

Whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (AVA) (Biothrax^®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (p < 0.0001) and among the racial categories (p < 0.0001). Controlling for covariates, the delayed cohort was non-inferior to the on-schedule cohort for the rate of 4-fold rise in both anti-PA IgG concentration (p < 0.0001) and TNA ED₅₀ titers (p < 0.0001); as well as the mean log₁₀-transformed anti-PA IgG concentration (p < 0.0001) and the mean log₁₀-transformed TNA ED₅₀ titers (p < 0.0001). Providing a missed AVA dose after a delay as long as 5–7 years, elicits anti-PA IgG antibody and TNA ED₅₀ responses that are robust and non-inferior to the responses observed when the 6-month dose is given on-schedule. These important data suggest it is not necessary to restart the series when doses of the anthrax vaccine are delayed as long as 5 or more years.     

Low serum serotype-specific pneumococcal antibody concentrations in young children with Haemophilus influenzae serotype b (Hib) vaccine failure

Serotype-specific pneumococcal antibody concentrations were measured in 164 children with Hib vaccine failure prior to routine pneumococcal immunisation. Compared with age-matched controls, a higher proportion of cases had non-protective antibody concentrations (<0.35 μg/ml) for 7/9 (78%) serotypes tested among 2–4 year-olds, 4/9 (44%) among 5–7 year-olds, 1/9 (11%) among 8–11 year-olds and 0/9 (0%) among 12–15 year-olds (χ² for trend = 14.0, p = 0.0002). Cases aged 2–4 years were also more likely to have non-protective antibody concentrations against more serotypes than controls, suggesting that children with Hib vaccine failure may have an intact but physiologically delayed ability to develop protective antibody concentrations against encapsulated organisms.     

Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age,a randomized controlled trial

Background

To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS).

Methods

Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS.

Findings

By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p < 0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p < 0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p < 0.001).

Interpretation

Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.     

Immunogenicity and safety of a second administration of 13-valent pneumococcal conjugate vaccine 5 years after initial vaccination in adults 50 years and older

BackgroundVaccination effectively reduces invasive disease and pneumonia caused by Streptococcus pneumoniae. However, waning antibody titers and the ability of revaccination to boost titers in older adults have been concerns. A study to describe antibody persistence after vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) and response to revaccination 5 years after the initial dose was conducted.MethodsPneumococcal vaccine–naive subjects aged 50–59 years were randomized and vaccinated with PCV13 plus trivalent inactivated influenza vaccine concomitantly or 1 month apart, then revaccinated with PCV13 five years later. Antipneumococcal polysaccharide opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) were determined before and approximately 1 month after each vaccination. Targeted local reactions and systemic events were collected for 14 days, adverse events (AEs) for 1 month, and serious AEs (SAEs) for 6 months after each vaccination.ResultsOf 1116 randomized subjects, 727 were revaccinated at year 5. Between the time of initial vaccination and revaccination, OPA GMTs and IgG GMCs declined but remained higher than levels before initial vaccination for 12 of the 13 vaccine serotypes. One month after revaccination, OPA GMTs and IgG GMCs were comparable with, or higher than, levels observed 1 month after initial vaccination for most vaccine serotypes. Local reactions were mostly mild. AEs were reported by <5% and SAEs by <1% of subjects at 1 and 6 months after revaccination, respectively. No SAEs were vaccine-related.ConclusionsRevaccination of adults ≥50 years with PCV13 five years after primary vaccination was safe and immunogenic. Additionally, antibody titers were maintained for at least 5 years after vaccination. The vaccine stimulated a memory response as shown by enhanced responses that were maintained or enhanced by revaccination.ClinicalTrials.gov registrationNCT00521586.     

Vaccine induced Hepatitis A and B protection in children at risk for cystic fibrosis associated liver disease

Objectives

Hepatitis A (HAV) and Hepatitis B (HBV) infections can cause serious morbidity in patients with liver disease, including cystic fibrosis associated liver disease (CFALD). HAV and HBV vaccinations are recommended in CFALD, and maintenance of detectable antibody levels is also recommended with chronic liver disease. A better understanding of factors predicting low HAV and HBV antibodies may help physicians improve protection from these viruses in CFALD patients.

Methods

We examined HAV and HBV vaccine protection in children at risk for CFALD. Clinical and vaccine histories were reviewed, and HAV and HBV antibody titers measured. Those with no vaccination history or low HAV or HBV titers received primary or booster vaccinations, and responses were measured.

Results

Thirty-four of 308 children were at risk for CFALD per project criteria. Ten had previous HAV vaccination, of which 90% had positive anti-HAV antibodies. Thirty-three of 34 had previously received primary HBV vaccination (most in infancy), but only 12 (35%) had adequate anti-HBs levels (≥10 mIU/mL). Children with adequate anti-HBs levels were older at first HBV vaccine (median 2.3 vs. 0.1 years, p < 0.01), and at final HBV vaccine (median 4.0 vs. 0.8 years, p = 0.01). Fourteen of 19 (74%) responded to HBV boosters. Z-scores for BMI at HBV booster were significantly lower in booster non-responders (p = 0.04).

Conclusions

Children at increased risk of CFALD have inadequate HAV and HBV antibody levels, and HBV antibody protection can be enhanced through vaccine boosters. HBV antibody titers should be assessed in CFALD patients with a history of vaccination, particularly in those who received HBV vaccines in infancy or who are malnourished.     

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls

Background

To evaluate co-administration of GlaxoSmithKline Biologicals’ human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).

Methods

This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n = 247), HepB (n = 247) or HPV co-administered with HepB (HPV + HepB; n = 247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.

Results

The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10 mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.

Conclusions

The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.

Clinical trials registration

ClinicalTrials.gov registration number NCT00652938.     

Trends in serotype prevalence in invasive pneumococcal disease before and after infant pneumococcal vaccination in Belgium, 2002–2010

Objectives

We evaluated the effect of the infant 7-valent pneumococcal conjugate vaccine (PCV7) program on the serotype distribution in invasive pneumococcal disease in the Belgian population.

Methods

Serotyping was performed on 13,998 bacteraemic and pleural fluid isolates sent to the National Reference Laboratory between 2002 and 2010. We compared the distribution of serogroups (SGs) between the pre- (2002–2004) and post-PCV7 (2007–2010) era for children (<18 years), adults (18–59 years) and older individuals (≥60 years).

Results

The proportion of cases caused by PCV7-SGs in subjects <18 years decreased from 69% pre-PCV7 to 26% post-PCV7 (p < 0.005) and the majority of cases caused by PCV7-SGs were caused by SG 19. Post-PCV7, the prevalence of PCV7-SGs decreased from 38% to 29% and from 57% to 35% in subjects in the age groups 18–59 and ≥60 years, respectively (p < 0.005). Post-PCV7 the prevalence of SGs 1, 7 and 19 increased significantly in subjects aged <18 years. The increase of SG19 was caused by an increase of serotype 19A in this age group (p < 0.005). After the introduction of infant PCV7 the largest rise in prevalence occurred for SGs 7, 12 and 22 (p < 0.005) in the two older age categories. Post PCV7, the overall PCV13 and 23-valent pneumococcal polysaccharide vaccine coverage rates decreased from 85% to 69% and from 96% to 93%, respectively (p < 0.005).

Conclusions

PCV7 has an impact on SG distribution of invasive pneumococcal disease isolates of vaccinated and unvaccinated subjects. SG replacement forms a major threat to the success of PCV7. PCV13, including several additional replacement serotypes (STs 1, 7F, 19A), represents an attractive alternative.     

Non-invasive pneumococcal serotypes and antimicrobial susceptibilities in a paediatric hospital in the era of conjugate vaccines

To evaluate the effects of 7-valent pneumococcal conjugate vaccine (PCV7) introduction to the routine childhood immunisation schedule in 2008 and its replacement by PCV13 in 2010 in Ireland, we surveyed the serotypes and antimicrobial susceptibilities of 339 pneumococci associated with carriage and non-invasive infection (NII) in a Dublin paediatric hospital from 2009 to 2012. Furthermore, we compared the distribution of pneumococcal serotypes collected from 2009 to 2012 to 105 NII pneumococci isolated in 2007, the year before conjugate vaccine introduction. PCV7 serotypes declined from 2007 to 2012 as follows: carriage, 67–23% (p = 0.0004); conjunctivitis, 58–0% (p < 0.0001); non-bacteraemic lower respiratory tract infection, 50–19% (p = 0.0363) and otitis media 54–27%. Notably, antimicrobial resistant (AMR) PCV7 serotypes showed a significant decrease by the end of the study period (i.e. 2012) (p < 0.0001). Compared with 2007 the overall occurrence of serotype 19A increased from 1.9 to 10% in 2010 (p = 0.0132) and to 15% in 2011 (p = 0.0005). Importantly, serotype 19A declined significantly from 2011 levels to an overall prevalence of 4.8% in 2012 (p = 0.0243). Most striking was the significant reduction of AMR 19A (p = 0.0195). Conversely, increases were observed in non-vaccine type (NVT) pneumococci in 2009–2012, of which serotypes 11A (n = 30), 15B/C (n = 17), 22F (n = 14), 35Bn = 13), non-typeable pneumococci (n = 13) and 23A (n = 12) were the most prevalent. Moreover, an increase in NVT non-susceptible to at least one antimicrobial in 2009–2012 was noted, attributable to serotypes 35B (n = 10) and 15A (n = 7). In summary, this study has shown that PCV7 and PCV13 introduction has had a positive impact on their target serotypes and antimicrobial resistance amongst pneumococci within a paediatric hospital within a short time period. However, the increase in NVT prevalence highlights the need for continued surveillance.