First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12 months and 5 years of age

Lindgren, Line M.; Tingskov, Pernille N.; Justesen, Annette H.; Nedergaard, Bettina; Olsen, Klaus J; Andreasen, Lars Vibe; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit

doi:10.1016/j.vaccine.2016.12.027

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…The first investigation of IPV-Al in adolescents supported this finding 16 . The low frequency of adverse events in this phase 2 trial suggests that a safety evaluation is not necessarily justified.…”

Section: Discussionmentioning

confidence: 71%

“…17 , 21 , 26 The first investigation of IPV-Al in adolescents supported this finding. 16 The low frequency of adverse events in this phase 2 trial suggests that a safety evaluation is not necessarily justified. Thus, a complete safety evaluation of IPV-Al will have to await the safety results from ongoing phase 3 trials.…”

Section: Discussionmentioning

confidence: 94%

“…The enrolled Danish adolescents, who were 10–15 years old, had a history of vaccination with IPV at 3, 5, and 12 months, and 5 years. The three IPV-Al vaccines were safe and all induced robust anamnestic responses as booster doses 16 . In the clinical trial reported here, the objective was to show the non-inferiority of the three vaccines compared with standard IPV, in infants vaccinated according to a primary vaccination schedule of 6, 10, and 14 weeks of age, as per the EPI.…”

Section: Introductionmentioning

confidence: 95%

“…The three IPV-Al vaccines were safe and all induced robust anamnestic responses as booster doses. 16 In the clinical trial reported here, the objective was to show the non-inferiority of the three vaccines compared with standard IPV, in infants vaccinated according to a primary vaccination schedule of 6, 10, and 14 weeks of age, as per the EPI. This is a challenging schedule for IPV, given the early age of the first vaccination and the short intervals between the doses, because high levels of maternal antibodies interfere with IPV immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial

Rivera¹,

Pedersen

Peña³

et al. 2017

The Lancet Infectious Diseases

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SummaryBackgroundCost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV.MethodsIn this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than −10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423.FindingsBetween Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations (ie, after completion of the expanded programme of immunisation schedule): 1/3 IPV-Al 98·5% (n=202, type 1), 97·6% (n=200; type 2), and 99·5% (n=204, type 3); 1/5 IPV-Al: 99·5% (n=204, type 1), 96·1% (n=197, type 2), and 98·5% (n=202, type 3); and 1/10 IPV-Al: 98·5% (n=201, type 1), 94·6% (n=193, type 2), and 99·5% (n=203, type 3). All three IPV-Al were non-inferior to IPV, with absolute differences in percentage seroconversion for each poliovirus type being greater than −10% (1/3 IPV-Al type 1, −1·46 [–3·60 to 0·10], type 2, −0·98 [–3·62 to 1·49], and type 3, −0·49 [–2·16 to 0·86]; 1/5 IPV-Al type 1, −0·49 [–2·16 to 0·86], type 2, −2·45 [–5·47 to 0·27], and type 3, −1·46 [–3·60 to 0·10]; and 1/10 IPV-Al type 1, −1·47 [–3·62 to 0·10], type 2, −3·94 [–7·28 to −0·97], and type 3, −0·49 [–2·17 to 0·86]). Three serious adverse events occurred that were unrelated to the vaccine.InterpretationThe lowest dose (1/10 IPV-Al) of the vaccine performed well both after two and three doses. Based on these results, this new vaccine is und...

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial

Rivera¹,

Pedersen

Peña³

et al. 2017

The Lancet Infectious Diseases

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“…Subsequently, seroconversion rates from fractional doses were shown to be adequate but somewhat lower than for full-dose intramuscular injection fractional doses [162,163,247]. Ironically, recent shortages in availability of IPV during transition from tOPV to bOPV [248] and safety issues during vaccine production have restimulated interest in use of fractional doses and new clinical trials for fractional doses, with and without use of adjuvants, and possible use of needle-free devices (non-inclusive example of recent references: [162,163,[249][250][251][252]).…”

Section: Poliovirus Infections At the Level Of The Individual Hostmentioning

confidence: 99%

Polio and Its Epidemiology

Shulman¹

2020

Encyclopedia of Sustainability Science and Technology

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AFP Acute flaccid paralysis. AFP surveillance Characterization of enteroviruses in stool samples from all AFP cases especially in individuals under 15 years of age to rule in or rule out etiology by polioviruses. AFR or AFRO The African Health Region of the WHO. AGG A PID with agammaglobulinemia. AMR or AMRO The American Health Region of the WHO. aVDPV A vaccine-derived poliovirus isolate whose evolutionary path is unknown or ambiguous. bOPV Bivalent oral polio vaccine (containing serotypes 1 and 3). BSL Biosafety standard level. CAG Containment Advisory Group. C-antigens Refers to the epitopes after poliovirus interacts with CD155 host cell receptor and transitions into a 135S particle. Capsid The protein shell that surrounds a virus particle. Capsomere One of the individual morphological units that makes up the viral capsid. It contains a single copy of viral capsid proteins VP1, VP| 2, VP3, and VP4. CAV Coxsackie A virus. CCID 50 The cell culture infectious dose of a virus that will cause cell death in 50% of replicate cell cultures. CDC US Centers for Disease Control and Prevention. CD155 or PVr The human encoded cell receptor for poliovirus, a member of the immunoglobulin superfamily. cDNA Complimentary DNA (DNA synthesized from RNA by a reverse transcriptase enzyme). CNS Central nervous system. Codon A sequence of three adjacent nucleotides on a strand of DNA or RNA that specifies which specific amino acid will be incorporated into a protein. Codon bias Unequal usage of synonymous codons (different codons that specify the same amino acid). CPE Cytopathic effect. CRE Cis-acting replication element. CVID Common variable immune deficiencya type of primary immune deficiency cVDPV A circulating vaccine-derived poliovirus, that is, a poliovirus that has evolved from vaccine during person-to-person transmission. D-antigens Refers to epitopes on native 150S virions. Lester M. Shulman has retired.

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Polio and Its Epidemiology

Shulman

2023

Encyclopedia of Sustainability Science and Technology Series

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First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12 months and 5 years of age

Abstract: HighlightsThree adjuvanted reduced dose IPV-Al SSI were safe and immunogenic in adolescents.The three IPV-Al SSI were highly immunogenic, but inferior to IPV Vaccine SSI as a booster.Reduced dose IPV-Al SSI is intended for markets in need of affordable IPV.

Cited by 9 publications

References 17 publications

Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial

Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial

Polio and Its Epidemiology

Polio and Its Epidemiology

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