Immunogenicity and safety of an adjuvanted inactivated polio vaccine,IPV-Al,following vaccination in children at 2, 4, 6 and at 15–18 months

BackgroundAvailability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV.MethodsA phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15–18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0).ResultsSeroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined −10%-point limit: 3.94% (-6.51; −2.01) for type 1; 0.0% (-1.30; −1.37) for type 2; −0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV.ConclusionsNon-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated.ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616.Funding: Bill & Melinda Gates Foundation.     

Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China

IntroductionReplacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China.MethodsIn pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N = 541) or OPV (N = 535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N = 470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study.ResultsStudy A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥94.7% IPV and ≥96.1% OPV recipients at 18–24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration.ConclusionTrivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile.     

Immunogenicity and safety of an adjuvanted inactivated polio vaccine,IPV-Al,compared to standard IPV: A phase 3 observer-blinded,randomised, controlled trial in infants vaccinated at 6, 10, 14 weeks and 9 months of age

BackgroundA dose-sparing inactivated polio vaccine (IPV-Al), obtained by adsorption of inactivated virus to an aluminium hydroxide adjuvant, can help mitigate global supply and the cost constraints of IPV. The objective of this trial was to demonstrate the non-inferiority of IPV-Al to standard IPV.MethodsThis phase 3, observer-blinded, randomised, controlled trial was conducted at 5 investigational sites in the Philippines. Infants not previously vaccinated with any polio vaccines were randomised to receive three IPV-Al (n = 502) or IPV vaccinations (n = 500) at 6, 10 and 14 weeks of age plus a booster vaccination at 9 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series.ResultsSeroconversion rates following primary vaccination with IPV-Al (483 infants in the per-protocol analysis set) or IPV (478 infants) were: polio type 1, 97.1% versus 99.0%; type 2, 94.2% versus 99.0%; and type 3, 98.3% versus 99.6%. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the predefined −10%-point limit: type 1, −1.85% (−3.85; −0.05); type 2, −4.75% (−7.28; −2.52); type 3, −1.24 (−2.84; 0.13). The booster effect (geometric mean titre (GMT) post-booster / GMT pre-booster) was: type 1, 63 versus 43; type 2, 54 versus 47; type 3, 112 versus 80. IPV-Al was well tolerated with a safety profile comparable to that of IPV. Serious adverse events were recorded for 29 infants (5.8%, 37 events) in the IPV-Al group compared to 28 (5.6%, 48 events) in the IPV group.ConclusionNon-inferiority of IPV-Al to IPV with respect to seroconversion was confirmed and a robust booster response was demonstrated. Both vaccines had a similar safety profile.ClinicalTrials.gov identifier: NCT03032419.     

Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age-a phase 3 extension to a randomised controlled trial

Background4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age.MethodsA phase 3, open label, multi-centre extension to a randomised controlled trial (ClinicalTrials.gov identifier NCT01717638) conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule.ResultsAt baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192).ConclusionWaning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.     

Immunogenicity and persistence from different 3-dose schedules of live and inactivated polio vaccines in Chinese infants

BackgroundOPV is the only poliovirus vaccine used in the China EPI system, although IPV is available in the private market. We compared immunigencity and persistence among different schedules of IPV and OPV.Methods536 Chinese infants were enrolled into 4 groups receiving different schedules administered at 2, 3, and 4 months of age: IPV–OPV–OPV, IPV–IPV–OPV, IPV–IPV–IPV, and OPV–OPV–OPV. The I–I–I group received an 18-month IPV booster dose. Blood samples were collected before the first dose, after the third dose, and at 18 months for all groups, and also after the booster dose for the I–I–I group. Polio neutralizing antibody titers were assessed, and seroprotection rates were calculated after primary immunization and at 18 months of age.ResultsBefore the first dose, GMTs of the 4 groups ranged from 2.96 to 6.89, and seroprotection rates ranged from 17.6% to 54.3%. After 3 doses, the GMT of the I–O–O and I–I–O groups ranged from 901.09 to 1,110.12, and the GMT of the I–I–I group range was 212.02 to 537.52, significantly lower than for the 2 sequential schedules (P < 0.001). Seroprotection rates were 98.1% to 100%, with no significant differences among groups. At 18 months of age, the GMTs declined to a range of 527.00 to 683.44 in the I–O–O and I–I–O groups, and declined to 150.04 to 239.89 in the I–I–I group, significantly lower than for the other 3 groups (P < 0.001).ConclusionsThe sequential schedules achieved high GMTs and seroprotection. The IPV-only schedule achieved high seroprotection but with lower GMTs. Sequential schedules are suitable for China. With the 2 sequential schedules, GMTs remained high at 18 months of age and were not inferior to the OPV-only schedule. Thus, with a sequential schedule, the booster dose could be given at 4 years of age, the same age as the current OPV booster dose.     

Immunogenicity of a low-dose diphtheria,tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria,tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap–IPV, Repevax^®; Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis^®; Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap–IPV, Tetravac^®; Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection.All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01 IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap–IPV, Tdap + OPV and DTap–IPV, respectively, had protective antitoxin levels greater than 0.1 IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV.Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.     

Effect of multiple,simultaneous vaccines on polio seroresponse and associated health outcomes

BackgroundAdministration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults.MethodWe retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent.ResultsThe >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p < 0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p > 0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p < 0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p > 0.1).ConclusionA combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations.     

The predicted persistence and kinetics of antibody decline 9 years after pre-school booster vaccination in UK children

BackgroundLong term follow-up of vaccine trials is essential to establish the duration of protection. In the context of worldwide concern about rising pertussis incidence, estimates of antibody persistence after vaccination, which do not account for the rise in antibody due to natural boosting or infection, may overestimate the degree of protection afforded by pertussis vaccines.MethodsThis was a 5 year follow up study of a randomised controlled trial of diphtheria, tetanus, pertussis and polio booster vaccines in UK children aged 3.5–5 years. Antibody persistence was measured at 1 month, 1, 3, and 5 years after vaccination and the kinetics of antibody decline were modelled longitudinally. Estimates of predicted antibody persistence 9 years after the pre-school booster were derived from model parameters.ResultsAntibody levels 9 years after vaccination were predicted to be above accepted thresholds for protection for diphtheria, tetanus and polio. Antibody responses to pertussis toxoid were undetectable in 49% of children at the 5 year follow up visit, and responses were predicted to be undetectable in 69% (95% CI 45–88%) of children by the time of their teenage booster at 13–14 years of age.ConclusionsThere is no defined correlate of protection for pertussis. However, the large proportion of participants in this study with undetectable pertussis antibody levels at both measured and predicted timepoints suggests sub-optimal immunity in adolescence. Adding pertussis to the teenage booster for UK children as is done in other countries, would enhance immunity in adolescence.     

Immune response to second vaccination series of hepatitis B virus among booster dose non-responders

ObjectiveTo evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination.Subjects and methodsAfter given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10 IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2^nd vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10 IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2^nd vaccination series.ResultsProtective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100 IU/L) and higher GMT (299.1 ± 3.6 IU/L) compared to those with undetectable 60% and 106.2 ± 12.9 IU/L respectively (P < 0.05). No significant difference was detected as regards gender or residence, P > 0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2^nd vaccination series.ConclusionA booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate.     

Long-term evaluation of mucosal and systemic immunity and protection conferred by different polio booster vaccines

Oral polio vaccine (OPV) and Inactivated Polio Vaccine (IPV) have distinct advantages and limitations. IPV does not provide mucosal immunity and introduction of IPV to mitigate consequences of circulating vaccine-derived polio virus from OPV has very limited effect on transmission and OPV campaigns are essential for interrupting wild polio virus transmission, even in developed countries with a high coverage of IPV and protected sewer systems. The problem is magnified in many countries with limited resources. Requirement of refrigeration for storage and transportation for both IPV and OPV is also a major challenge in developing countries. Therefore, we present here long-term studies on comparison of a plant-based booster vaccine, which is free of virus and cold chain with IPV boosters and provide data on mucosal and systemic immunity and protection conferred by neutralizing antibodies.Mice were primed subcutaneously with IPV and boosted orally with lyophilized plant cells containing 1 μg or 25 μg polio viral protein 1 (VP1), once a month for three months or a single booster one year after the first prime. Our results show that VP1-IgG1 titers in single or double dose IPV dropped to background levels after one year of immunization. This decrease correlated with >50% reduction in seropositivity in double dose and <10% seropositivity in single dose IPV against serotype 1. Single dose IPV offered no or minimal protection against serotype 1 and 2 but conferred protection against serotype 3. VP1-IgA titers were negligible in IPV single or double dose vaccinated mice. VP1 antigen with two plant-derived adjuvants induced significantly high level and long lasting VP1-IgG1, IgA and neutralizing antibody titers (average 4.3–6.8 log2 titers). Plant boosters with VP1 and plant derived adjuvants maintained the same level titers from 29 to 400 days and conferred the same level of protection against all three serotypes throughout the duration of this study. Even during period, when no plant booster was given (∼260 days), VP1-IgG1 titers were maintained at high levels. Lyophilized plant cells expressing VP1 can be stored without losing efficacy, eliminating cold chain. Virus-free, cold-chain free vaccine is ready for further clinical development.     

Is there an association between the coverage of immunisation boosters by the age of 5 and deprivation? An ecological study

ObjectiveTo determine whether there was an association between the coverage of booster immunisation of Diphtheria, Tetanus, acellular Pertussis and Polio (DTaP/IPV) and second Measles, Mumps and Rubella (MMR) dose by age 5 in accordance with the English national immunisation schedule by area-level socioeconomic deprivation and whether this changed between 2007/08 and 2010/11.DesignEcological study.DataRoutinely collected national Cover of Vaccination Evaluated Rapidly data on immunisation coverage for DTaP/IPV booster and second MMR dose by age 5 and the Index of Multiple Deprivation (IMD).SettingPrimary Care Trust (PCT) areas in England between 2007/08 and 2010/11.Outcome MeasuresPopulation coverage (%) of DTaP/IPV booster and second MMR immunisation by age 5.ResultsOver the 4 years among the 9,457,600 children there was an increase in the mean proportion of children being immunised for DTaP/IPV booster and second MMR across England, increasing from 79% (standard deviation (SD12%)) to 86% (SD8%) for DTaP/IPV and 75% (SD10%) to 84% (SD6%) for second MMR between 2007/08 and 2010/11. In 2007/08 the area with lowest DTaP/IPV booster coverage was 31% compared to 54.4% in 2010/11 and for the second MMR in 2007/08 was 39% compared to 64.8% in 2010/11. A weak negative correlation was observed between average IMD score and immunisation coverage for the DTaP/IPV booster which reduced but remained statistically significant over the study period (r = −0.298, p < 0.001 in 2007/08 and r = −0.179, p = 0.028 in 2010/11). This was similar for the second MMR in 2007/08 (r = −0.225, p = 0.008) and 2008/09 (r = −0.216, p = 0.008) but there was no statistically significant correlation in 2009/10 (r = −0.108, p = 0.186) or 2010/11 (r = −0.078, p = 0.343).ConclusionLower immunisation coverage of DTaP/IPV booster and second MMR dose was associated with higher area-level socioeconomic deprivation, although this inequality reduced between 2007/08 and 2010/11 as proportions of children being immunised increased at PCT level, particularly for the most deprived areas. However, coverage is still below the World Health Organisation recommended 95% threshold for Europe.     

Vaccine effectiveness of PCV13 in a 3 + 1 vaccination schedule

ObjectiveTo assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3 + 1 schedule in Germany.MethodsActive surveillance for IPD in children <16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.ResultsData on 164/304 reported IPD cases were informative and met the inclusion criteria. VE for the extra six serotypes was 88% [95% confidence interval (CI): 73; 95] and 83% [56; 94] for at least one and for at least two doses respectively. VE for the complete 3 + 1 vaccination schedule was not conclusive because of a wide 95% CI. For serotype 3 VE appeared to be zero with an even wider 95% CI.ConclusionPCV13 VE against the extra six serotypes with the 3 + 1 schedule in Germany was only marginally higher compared to previously published data for the 2 + 1 schedule.     

Extensive swelling of the limb and systemic symptoms after a fourth dose of acellular pertussis containing vaccines in England in children aged 3–6 years

Extensive limb swelling (ESL) after a booster dose of acellular pertussis (aP) containing vaccine can cause concern and has the potential to be confused with cellulitis. In the United Kingdom aP-containing vaccine was introduced for primary immunisation at 2, 3 and 4 months of age in 2004, with the first cohorts eligible to receive a fourth dose in 2007 at school entry. We assessed the frequency of ESL (here defined as swelling >100 mms diameter) in 973 children receiving a fourth dose of one of four aP vaccines given combined with inactivated polio, tetanus and either low dose diphtheria (TdaP/IPV) or high dose diphtheria (DTaP/IPV) vaccine; 2 of the 3 DTaP/IPV vaccines also contained Haemophilus influenza b conjugate vaccine (Hib). Post-vaccination symptoms and local reactions were recorded in 7-day diaries or by a telephone follow up if no diary was returned. Local swellings >50 mm diameter were reported by 2.2% TdaP/IPV recipients compared with 6.6–11.1% of DTaP/IPV recipients; the corresponding proportions for redness >50 mms was 7.0% for TdaP/IPV and 13.3–17.7% for DTaP/IPV recipients. Among the latter, the addition of Hib did not affect the frequency or size of local reactions. Pain at the injection site and systemic symptoms did not differ between the four vaccine groups. A history of atopy was not associated with development of local swelling or redness. A total of 13 children (1.3%) experienced an ESL, three after TdaP/IPV. ESLs resolved without systemic upset within a few days and were usually painless; medical advice was only sought for two children. Parents should be informed about the possible occurrence of an ESL with the pre-school aP-containing booster vaccine but can be reassured that it is a benign and transient condition.     

Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: A randomized controlled clinical trial

BackgroundHighly pathogenic avian influenza A/H5N1 viruses continue to circulate in birds and infect humans causing serious illness and death.MethodsIn this randomized, observer-blinded study, adults ≥18 years of age (n = 841) received 3.75 or 7.5 μg hemagglutinin antigen (HA) of an AS03-adjuvanted (AS03_A or AS03_B) A/Indonesia/5/2005 H5N1 (subclade 2.1) vaccine (priming), followed by the same HA dose of AS03-adjuvanted A/turkey/Turkey/1/05 H5N1 (clade 2.2) influenza vaccine as a booster 6 or 18 months after priming; an unprimed group received placebo at Day 0, and 3.75 μg HA of AS03_A-adjuvanted booster vaccine at 6 and 18 months. Antibody responses were assessed by hemagglutination-inhibition assay (HI). Microneutralization (MN) antibody and cellular immunoassays were assessed in a subset of participants.ResultsGeometric mean titers (GMTs) and seroconversion rates (SCRs) were higher in primed vs. unprimed subjects against the booster strain 10 days following booster vaccination at month 6 and month 18. After the booster at 18 months, the lower limit of the 97.5% confidence interval for the difference in SCR and GMT ratios between primed and unprimed subjects was >15% and >2.0, respectively, fulfilling the primary endpoint criteria for superiority against the booster strain. MN and cellular immune responses corresponded with the immunogenicity seen in HI measures.ConclusionsAdults primed with a dose-sparing oil-in-water adjuvanted H5N1 subclade vaccine had rapid and durable antibody responses to a heterologous subclade boosting vaccine given 6 or 18 months later.     

Needle adapters for intradermal administration of fractional dose of inactivated poliovirus vaccine: Evaluation of immunogenicity and programmatic feasibility in Pakistan

Administration of 1/5th dose of Inactivated poliovirus vaccine intradermally (fIPV) provides similar immune response as full-dose intramuscular IPV, however, fIPV administration with BCG needle and syringe (BCG NS) is technically difficult. We compared immune response after one fIPV dose administered with BCG NS to administration with intradermal devices, referred to as Device A and B; and assessed feasibility of conducting a door-to-door vaccination campaign with fIPV. In Phase I, 452 children 6–12 months old from Karachi were randomized to receive one fIPV dose either with BCG NS, Device A or Device B in a health facility. Immune response was defined as seroconversion or fourfold rise in polio neutralizing antibody titer 28 days after fIPV among children whose baseline titer ≤362. In Phase II, fIPV was administered during one-day door-to-door campaign to assess programmatic feasibility by evaluating vaccinators’ experience. For all three poliovirus (PV) serotypes, the immune response after BCG NS and Device A was similar, however it was lower with Device B (34/44 (77%), 31/45 (69%), 16/30 (53%) respectively for PV1; 53/78 (68%), 61/83 (74%), 42/80 (53%) for PV2; and; 58/76 (76%), 56/80 (70%), 43/77 (56%) for PV3; p < 0.05 for all three serotypes). Vaccinators reported problems filling Device B in both Phases; no other operational challenges were reported during Phase II. Use of fIPV offers a dose-saving alternative to full-dose IPV.     

Effect of booster doses of poliovirus vaccine in previously vaccinated children,Clinical Trial Results 2013

BackgroundConsidering the current polio situation Pakistan needs vaccine combinations to reach maximum population level immunity. The trial assessed whether inactivated poliovirus vaccine (IPV) can be used to rapidly boost immunity among children in Pakistan.MethodsA five-arm randomized clinical trial was conducted among children (6–24 months, 5–6 years and 10–11 years). Children were randomized in four intervention arms as per the vaccines they received (bOPV, IPV, bOPV + vitamin A, and bOPV + IPV) and a control arm which did not receive any vaccine. Baseline seroprevalence of poliovirus antibodies and serological immune response 28 days after intervention were assessed.ResultsThe baseline seroprevalence was high for all serotypes and the three age groups [PV1: 97%, 100%, 96%, PV2: 86%, 100%, 99%, PV3: 83%, 95%, 87% for the three age groups respectively]. There was significantly higher rate of immune response observed in the study arms which included IPV (95–99%) compared with bOPV only arms (11–43%), [p < 0.001]; Vitamin A was not associated with improved immune response. Immune response rates in the IPV only arm and IPV + bOPV arm were similar [p > 0.5].ConclusionIPV has shown the ability to efficiently close existing immunity gaps in a vulnerable population of children in rural Pakistan.     

Travel medicine consultation: An opportunity to improve coverage for routine vaccinations

BackgroundTravelers may be responsible for the spread of vaccine-preventable diseases upon return. Travel physicians and family physicians may play a role in checking and updating vaccinations before traveling. Our aim was to evaluate the vaccine coverage for mandatory and recommended vaccination in travelers attending a travel medicine clinic (TMC).MethodsVaccine coverage was measured using the current French immunization schedule as reference for correct immunization, in travelers providing a vaccination certificate during the TMC visit (university hospital of Saint-Étienne), between August 1, 2013 and July 31, 2014.ResultsIn total, 2336 travelers came to the TMC during the study period. Among the 2019 study participants, only 1216 (60.3%) provided a vaccination certificate. Travelers who provided a vaccination certificate were significantly younger than travelers who did not (mean age: 34.8 ± 17.8 vs. 46 ± 18.4 years, P < 0.005) and were less likely to be Hajj pilgrims. Vaccine coverage against Tetanus, Diphtheria, and Poliomyelitis (Td/IPV vaccine) was 91.8%, 78.6% against Measles, Mumps, and Rubella (MMR), and 59.4% against Viral Hepatitis B (HBV). BCG vaccine coverage was 71.9%. Older travelers were less likely to be correctly vaccinated, except against HBV as vaccinated travelers were significantly older than unvaccinated travelers.ConclusionObtaining information about immunization in travelers is difficult. Coverage for routine vaccines should be improved in this population. Travel medicine consultations could be the opportunity to vaccinate against MMR, HBV, and Td/IPV.     

The doses of 10 μg should replace the doses of 5 μg in newborn hepatitis B vaccination in China: A cost-effectiveness analysis

ObjectiveTo identify whether Chinese current series of three 5 μg doses for newborn hepatitis B vaccination should be replaced by the series of three 10 μg doses.MethodsA cost-effectiveness analysis was conducted from the societal perspective based on the constructed decision tree-Markov model. Model parameters were estimated from published literatures, government documents and our surveys. The expected cost and effectiveness were compared between the 3-dose 5 μg series (the 5 μg strategy) and the 3-dose 10 μg series (the 10 μg strategy), and the incremental cost-effectiveness ratio (ICER, additional cost per quality-adjusted life-years gained) was calculated. Threshold values of the efficacy difference of the two series for the ICER = 0, 1 and 3 times per capita gross domestic product were analyzed under different scenarios to understand whether the 10 μg strategy should replace the 5 μg strategy according to the recommendation of World Health Organization.ResultsThe 10 μg strategy would be cost-saving compared with the 5 μg strategy under the base-case scenario. Under keeping all the other parameters at the base-case values or further adjusting any one of them to the value most unfavorable to the 10 μg strategy, as long as the efficacy of 3-dose 10 μg series was slightly higher than that of 3-dose 5 μg series, the 10 μg strategy would be cost-effective, highly cost-effective, or even cost-saving. Even under the most pessimistic scenario, i.e. all the other parameters, but the discount rate, at the values most unfavorable to the 10 μg strategy, the 10 μg strategy would be cost-effective if the efficacy difference reached higher than 1.23 percentage point.ConclusionFor newborn hepatitis B vaccination in China, the 10 μg strategy should be cost-effective, even more possibly highly cost-effective or cost-saving compared with the current 5 μg strategy. The doses of 10 μg should be considered to replace the doses of 5 μg in newborn hepatitis B vaccination in China.