Liquid Hexavalent Vaccine Research Articles

Parents' and healthcare professionals' perception toward the introduction of a new fully liquid hexavalent vaccine in the Malaysian national immunization program: a cross-sectional study instrument development and its application.

A newly developed fully liquid hexavalent vaccine that comprises six antigens for Diphtheria, Tetanus, acellular Pertussis, Inactivated Poliomyelitis, Haemophilus Influenza type b., and Hepatitis B, is proposed to be introduced in the Malaysian national immunization program, instead of the non-fully liquid pentavalent vaccine and monovalent Hepatitis B vaccine that is currently employed in the immunization schedule. Although the introduction of new vaccines is a necessary intervention, it still needs to be accepted by parents and healthcare professionals. Hence, this study aimed to develop three structured questionnaires and to investigate the participants' perception and acceptability toward the incorporation of the new fully liquid hexavalent vaccine. A cross-sectional study was conducted among a sample of 346 parents, 100 nurses, and 50 physicians attending twenty-two primary health care centers in the states of Selangor and the Federal Territory of Kuala Lumpur and Putrajaya during 2019-2020. The study found that Cronbach's alpha coefficients for the study instruments ranged from 0.825 to 0.918. Principal components analysis produced a good fit with KMO>0.6. For the parents' perception questionnaire, the only extracted factor explained 73.9 % of the total variance; for the nurses' perception toward a non-fully and fully liquid combined vaccine, there was a sole extracted factor that explained 65.2 % and 79.2% of the total variance, respectively. Whereas for the physicians' perception, there was one factor extracted that explains 71.8 % of the total variance. The median score for all the questionnaire items ranged from 4 to 5 (Q1 and Q3 vary between 3-5). Parents' ethnicity was significantly associated (P-value ≤ 0.05) with the perception that the new hexavalent vaccine would reduce their transportation expenses. Moreover, a significant association (P-value ≤ 0.05) was found between physicians' age and the perception of the hexavalent vaccine's ability to decrease patient overcrowding in primary healthcare centers. The instruments used in this study were valid and reliable. Parents of Malay ethnicity were the most concerned about transportation expenses since they have the lowest income and are more concentrated in rural areas compared to other races. Younger physicians were concerned about reducing patient crowding and hence reducing their workload and burnout.

PIN13 Cost-Minimization Analysis of Introducing Hexaxim® into Korean National Immunization Program

Multivalent vaccines have brought public health and economic benefits by covering new antigens without increasing the number of injections. A fully liquid hexavalent vaccine, Hexaxim® (DTaP-IPV-Hib-HepB) has been approved in Korea with proven immunogenicity and safety compared to pentavalent DTaP-IPV/Hib co-administered with standalone Hep B vaccine. This research aims to evaluate the socio-economic impact of introducing Hexaxim® in Korean national immunization program (NIP). A cost-minimization analysis was performed with a societal perspective over a 1-year time horizon. Vaccines acquisition, administration, immunization error related costs, parents’ transportation and time costs were considered in the model. The probabilities of immunization error were obtained from Time and Motion study, which showed that a fully liquid vaccine significantly reduced the preparation time and resulted in fewer immunization errors. Data on birth cohort, vaccine coverage rate, transportation cost and hourly gross wage were collected from official national sources. In order to obtain the number of hospital visits for inoculation, a nationwide online market research (N=400) was carried out in August 2020. Parents’ time costs were estimated by Opportunity Cost Methods, but different approaches also explored in the sensitivity analysis. If Korea switches from the current pentavalent DTaP-IPV/Hib plus HepB to Hexaxim® for NIP, it will provide 33.2 billion KRW (=29 million USD) substantial cost-savings over the coming year. This was mainly attributable to parents’ time savings by reducing hospital visits. Reducing transportation, inoculation fee and immunization errors were also contributing factors. Sensitivity analyses indicated that results were robust to the different valuation approaches. Our research demonstrates the socio-economic value of Hexaxim® beyond clinical evidences. Additional practical benefits of Hexaxim® such as reducing storage, distribution and preparation steps, which were not fully captured in this analysis, could be considered from HCP’s perspectives. These results would support evidence-based decision-making on the introduction of Hexaxim® in Korea NIP.

Immunogenicity and safety of a hexavalent pediatric vaccine in HIV-exposed infected and uninfected infants in Republic of South Africa

ABSTRACT Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15–18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.

What are the preferences of health care professionals in Germany regarding fully liquid, ready-to-use hexavalent pediatric vaccine versus hexavalent pediatric vaccine that needs reconstitution?

Diphtheria, tetanus and acellular pertussis (DTaP) based combined vaccines have led to significant reduction in incidence of several serious pediatric infectious diseases. A new, fully liquid combined hexavalent vaccine has been introduced and has been shown to reduce administration time. This fully liquid vaccine may also be simpler to administer and could reduce handling errors. The present study was designed to understand the value that health care providers (HCPs) place on aspects of injection devices for combined hexavalent vaccine programs in Germany. A discrete choice experiment (DCE) was designed to elicit the views of HCPs regarding hexavalent vaccines. The key attributes of injection devices were identified through a focused literature search and interviews with HCPs. Five key attributes, each with two or three levels were described which included: type of device, experience of this hexavalent vaccine on the German market, preparation time, probability of handling errors, and dosage errors. Physicians (n=150) and nurses (n=150) who administered hexavalent vaccines in Germany completed the survey. Choice data were analyzed using the conditional logit procedure. All attributes were significant and important independent influences on physicians’ and nurses’ choices. Reducing any “probability of dosage errors” was the most important attribute. Both physicians and nurses had a strong preference to reduce preparation time. All other things equal both groups also significantly preferred a fully liquid hexavalent vaccine. They also preferred vaccines that had been on the market for a few years compared to ones that had not (especially the physicians). Additional analyses explored participants’ preferences in more detail through interaction terms. The DCE choice data provide useful insights into how HCPs view each aspect of the vaccination device. Overall, the HCPs preferred fully liquid vaccines. The survey also highlighted the importance of handling and dosage errors, reducing preparation time, and also experience of the HCPs with the use of a vaccine. The survey work included physicians and nurses and explored their views separately.

Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study

Background and aimsSimplified vaccine preparation steps would save time and reduce potential immunisation errors. The aim of the study was to assess vaccine preparation time with fully-liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD) versus non-fully liquid hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals). MethodsNinety-six Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, time and motion study in Belgium (2014). HCPs prepared each vaccine in a cross-over manner with a wash-out period of 3–5min. An independent nurse assessed preparation time and immunisation errors by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire. ResultsAverage preparation time was 36s for the fully-liquid vaccine and 70.5s for the non-fully liquid vaccine. The time saved using the fully-liquid vaccine was 34.5s (p≤0.001). On 192 preparations, 57 immunisation errors occurred: 47 in the non-fully liquid vaccine group (including one missing reconstitution of Hib component), 10 in the fully-liquid vaccine group. 71.9% of HCPs were very or somewhat satisfied with the ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in the fully-liquid vaccine and the non-fully liquid vaccine groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of the fully-liquid vaccine in their daily practice. ConclusionsPreparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors.

O-147a Assessment Of Preparation Time With Fully Liquid Versus Reconstituted Paediatric Hexavalent Vaccines. A Time And Motion Study

<h3>Background and aims</h3> Simplified vaccine preparation steps would save time and reduce the potential of mishandlings. The aim of the study was to assess vaccine preparation time with fully liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD, Lyon, France) versus hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals, Rixensart, Belgium). <h3>Methods</h3> 96 Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, Time and Motion study in Belgium (2014). HCPs prepared each vaccine (time recorded using video equipment) in a cross-over manner with a wash-out period of 3–5 min. An independent nurse assessed preparation mishandlings by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire. <h3>Results</h3> Average preparation time was 36 seconds for DTaP-IPV-HB-PRP-T versus 70.5 seconds for DTPa-HBV-IPV/Hib (p ≤ 0.001). Extrapolated yearly time savings was estimated to 664 days/year (based on 520 000 hexavalent vaccines administered per year in Belgium). On 192 preparations, 57 mishandlings occurred: 47 in the DTPa-HBV-IPV/Hib group (including one missing reconstitution of Hib component), 10 in the DTaP-IPV-HB-PRP-T group. 71.9% of HCPs were very or somewhat satisfied with ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in DTaP-IPV-HB-PRP-T and DTPa-HBV-IPV/Hib groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of DTaP-IPV-HB-PRP-T vaccine in their daily practice. <h3>Conclusions</h3> Fully liquid DTaP-IPV-HB-PRP-T vaccine offers significant time gains for vaccine preparation. It has the potential to reduce mishandlings and could therefore be very useful in daily practice.

Economic assessment of implementing Hexaxim® vaccine within the South African Expanded Programme on Immunisation (EPI-SA)

Background: The South African Expanded Programme on Immunisation (EPI-SA) currently vaccinates against 10 childhood vaccine preventable diseases. Six injections are required for primary vaccination against diphtheria, tetanus, pertussis, polio, Haemophilus influenza type b and hepatitis B: three DTaP-IPV//Hib [Pentaxim] doses and three monovalent Hep B vaccines to children under 12 months of age, with a seventh injection (Pentaxim booster) at 18 months. Madhi et al (PIDJ 30:e68 2011) demonstrated no significant difference in the safety and efficacy between Pentaxim plus monovalent Hep B and a new fully liquid hexavalent vaccine, Hexaxim (DTaP-IPV-Hib-HepB). Fromahealthcare provider perspective, combination vaccines could reduce costs, simplify logistics anddelivery infrastructure, and improvecoverage with fewer injections. This study aimed to analyse the cost implications of a switch from the current combination of Pentaxim plus monovalent Hep B injections, to a single Hexaxim injection, from the public sector perspective. Methods & Materials: Data were collected to derive direct costs, i.e. vaccines’ prices (except Hexaxim, no price yet available), transportation charges, cold chain storage, vaccine wastage rate, hazardouswastedisposal andvaccineadministration.All costs were calculated per dose, and expressed in South African Rand (R) (USD 1.00=R10.19 per 2013 exchange rate). Indirect costs such as individual and societal benefits were excluded. Results: Delivering one dose ofPentaxim and Hep B costs R166.30. Reduced volumes result in cost reductions when using Hexaxim for: cold storage; hazardous waste disposal; and vaccine administration, resulting in an estimated saving of R10.52 to R29.40 per dose, depending on utilisation of usable cold storage space. Conclusion: Implementation of Hexaxim within EPI-SA is highly recommended, because it reduces healthcare provider costs by simplifying logistics and delivery infrastructure. From a community perspective, such vaccines reduce clinic visits, vaccinators’ errors, number of injections and side effects,which translate to better acceptability, convenience and increased compliance. As theuse of Hexaxim demonstrates direct and indirect cost savings, potential public sector introduction should be valued not only in terms of the price of Pentaxim and Hep B.

Antibody Persistence and Booster Vaccination of a Fully Liquid Hexavalent Vaccine Coadministered With Measles/Mumps/Rubella and Varicella Vaccines at 15–18 Months of Age in Healthy South African Infants

To assess antibody persistence and booster immunogenicity and safety of a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine. Phase III, open-label, 2-center trial. Infants previously primed at 6, 10, 14 weeks of age with DTaP-IPV-Hep B-PRP-T either without (group 1: N = 218) or with hepatitis B at birth (group 3: N = 130) or control DTwP-Hib, hepatitis B and oral poliovirus vaccine vaccines (group 2: N = 219) received the same vaccine(s) as booster (except hepatitis B for group 2) at 15-18 months of age, coadministered with measles/mumps/rubella and varicella vaccines (MMR+V). All participants had received measles vaccine at 9 months of age. Antibodies were measured prebooster and 1 month postbooster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. Antibody persistence (seroprotection and concentration) at 15-18 months of age was high for each valence and similar in each group, except for Hep B (highest in group 3 [extra dose of hepatitis B]) and PRP (highest in group 2). Postbooster seroprotection (D, T, IPV, Hep B, PRP) and seroconversion (pertussis toxin and filamentous hemagglutinin) rates were high and similar in each group (excluding Hep B in group 2 [no booster]); geometric mean antibody levels increased markedly in all groups. The response to MMR+V was similar in each group. All vaccines were well tolerated. A booster dose of the new DTaP-IPV-Hep B-PRP-T vaccine at 15-18 months of age is highly immunogenic and safe compared with licensed comparators, following primary series administration in the Expanded Program on Immunization schedule, with or without a hepatitis B vaccine at birth and coadministered with MMR+V.

Administration of hepatitis A vaccine at 6 and 12 months of age concomitantly with hexavalent (DTaP–IPV–PRP∼T–HBs) combination vaccine

Background Administration of two doses of hepatitis A (HA) vaccine to children ≥2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age. Methods In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC ®) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA ®) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age). Results HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered. Conclusions A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age.

Safety and Immunogenicity of Two Formulations of a Hexavalent Diphtheria-Tetanus-Acellular Pertussis-Inactivated Poliovirus-Haemophilus influenzae b Conjugate-Hepatitis B Vaccine in 15 to 18 Month-Old Children

Combination vaccines decrease the number of injections and improve parental satisfaction and vaccination schedule compliance. In a phase 1, randomized, partially-blinded, single-dose booster study, we evaluated two formulations of an investigational liquid hexavalent vaccine containing diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate and hepatitis B surface antigen (DTaP-IPV-Hib-HBV) in 60 healthy toddlers, 15 to 18 months of age who had been primed with three doses of a licensed pentavalent diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate (DTaP-IPV//PRP-T) vaccine. The DTaP-IPV//PRP-T vaccine was used as a control in 30 subjects. The investigational formulations, which contained the same DTaP-IPV components, differed only in Hib (content and conjugate) and HBV (content) (PRP-T/HBV10=12 Fg Hib tetanus toxoid conjugate with 10 Fg HBsAg; PRP-OMPC/HBV15=6 Fg Hib Neisseria meningitidis outer membrane protein complex with 15 Fg HBsAg). Injection-site pain, redness, and swelling were reported by 46.7%, 46.7%, and 20.0% of the licensed vaccine recipients, 43.3%, 43.3%, and 26.7% of PRP-T/HBV10 recipients and 70.0%, 46.7%, and 46.7% of PRP-OMPC/HBV15 recipients, respectively. Fever $37.8EC and irritability were reported by 0% and 16.7% of licensed vaccine recipients, 10.3% and 23.3% of PRP-T/HBV10 recipients and 30.0% and 16.7% of PRP-OMPC/HBV15 recipients, respectively. There were no apparent differences between the groups in the proportion of participants achieving pre-defined, threshold or seroprotective immune responses. Geometric mean antibody levels for all antigens were similar except for anti-PRP levels, which were 19.0 Fg/mL in recipients of the licensed vaccine, 40.8 Fg/mL in PRP-T/HBV10 recipients, and 9.4 Fg/mL in PRP-OMPC/HBV15 recipients. We conclude that the hexavalent formulations appear generally well tolerated and immunogenic as a booster dose in these toddlers.

Large scale safety study of a liquid hexavalent vaccine (D-T-acP–IPV–PRP∼T–HBs) administered at 2, 4, 6 and 12–14 months of age

A study was conducted to assess the safety of a new, liquid hexavalent vaccine (Hexavac ®, Aventis Pasteur MSD, Lyon, France) in a large population of 1783 children in Germany vaccinated at 2, 4, 6 and 12–14 months of age. Immediate reactions, local and systemic reactions, and serious adverse events (SAEs) were monitored. The frequencies of redness ≥2 cm and swelling ≥2 cm were 6.7 and 7.1% after all doses of the primary series combined and 13.4 and 12.0% following the booster dose, respectively. Transient swelling of the entire thigh was reported in seven infants after all doses of the primary series (0.1%) and in four children after the booster dose (0.2%). The most frequent systemic adverse events within 3 days after vaccination were irritability (19.3% after primary series and 13.2% after booster) and fever ≥38.0°C (15.4% after primary series and 28.5% after booster). Fever above 40.0°C was reported in 0.1% of the infants post-primary series and in 0.9% of the children after the booster immunization. Only 3 of 144 SAE were considered to be vaccine related and were seen to resolve spontaneously and without sequelae. The liquid hexavalent vaccine was generally well tolerated when given to children as a primary immunization series at 2, 4 and 6 months and as a booster dose at 12–14 months.