Hexavalent vaccinations: The future of routine immunization?

Shashidhar, A

doi:10.1007/s13312-017-0988-3

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Also, Indian Pediatrics published an editorial entitled "Hexavalent vaccinations: The future of routine immunization?" (17), which suggested that this combined vaccine was being promoted for India. It is crucial that the regulatory authority in India is aware of the concerns raised in this commentary on the PSUR reports.…”

Section: Relevance To Indiamentioning

confidence: 99%

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency

Puliyel

Sathyamala²

2017

IJME

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There have been a number of spontaneous reports of sudden unexpected death soon after the administration of Infanrix hexa (combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenza type B vaccine). The manufacturer, GlaxoSmithKline (GSK), submits confidential periodic safety update reports (PSURs) on Infanrix hexa to the European Medicines Agency (EMA). The latest is the PSUR 19. Each PSUR contains an analysis of observed/expected sudden deaths, which shows that the number of observed deaths soon after immunisation is lower than that expected by chance. This commentary focuses on that aspect of the PSUR which has a bearing on policy decisions. We analysed the data provided in the PSURs. It is apparent that the deaths acknowledged in the PSUR 16 were deleted from the PSUR 19. The number of observed deaths soon after vaccination among children older than one year was significantly higher than that expected by chance once the deleted deaths were restored and included in the analysis. The manufacturer must explain the figures that have been submitted to the regulatory authorities. The procedures undertaken by the EMA to evaluate the manufacturer's claims in the PSUR need to be reviewed. The Drugs Controller General of India nearly automatically accepts drugs and vaccines approved by the EMA. There is a need to reappraise the reliance on due diligence by the EMA.

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Section: Relevance To Indiamentioning

confidence: 99%

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency

Puliyel

Sathyamala²

2017

IJME

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“…The use of combined vaccines simplifies vaccination programs while reducing implementation costs and is considered as a valuable approach in improving immunization coverage 3 – 5 . Also, vaccines combining Inactivated Poliomyelitis vaccine (IPV) are of great public health importance in the view of WHO’s Strategic Advisory Group of Experts recommendation to introduce IPV in the immunization programs 6 .…”

Section: Introductionmentioning

confidence: 99%

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants

Sharma,

Parekh,

Pujari

et al. 2024

npj Vaccines

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A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration – CTRI/2019/11/022052

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“…Combination vaccines provide additional societal benefits for families and healthcare providers including improved compliance (i.e., completion of the entire vaccination series) and higher productivity (i.e., fewer visits save time and money) [ 2 ]. Overall, worldwide implementation of combination vaccines has enhanced global vaccine access and immunization coverage, especially in low- and middle- income countries (LMICs) [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The pediatric combination vaccine comprising diphtheria and tetanus toxoids and inactivated whole-cell pertussis bacteria (DTwP) has played an important role in protecting the global pediatric population for over half a century [ 1 ]. Although the reactogenicity profile of this vaccine has been improved by replacing wP with aP (acellular pertussis) antigens, the latter vaccine has primarily been used in high-income countries due to (1) the high cost of manufacturing five different aP antigens [ 1 ] and (2) the observation that vaccines containing aP antigens display more rapid waning of immunity against pertussis infection compared to vaccines containing the wP antigen [ 4 , 5 ]. Based on these considerations, pediatric combination vaccines containing wP are primarily used in LMICs and are formulated as multidose presentations to further lower costs [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

Kumar,

Holland,

Secrist

et al. 2024

Vaccines

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Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.

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Hexavalent vaccinations: The future of routine immunization?

Cited by 5 publications

References 13 publications

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

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