Delving into the Latest Updates on Hepatitis A inactivated & hepatitis B (recombinant) vaccine(GlaxoSmithKline Plc) with Synapse

Overview

Basic Info

Drug Type

Inactivated vaccine, Prophylactic vaccine

Synonyms

Ambirix, Hepatitis A-hepatitis B vaccine, Twinrix Adult

+ [6]

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis AHepatitis B

Inactive Indication-

Originator Organization

GSK Plc

Active Organization

GlaxoSmithKline Biologicals SAGlaxoSmithKline LLC

Inactive Organization

GSK Plc

Drug Highest PhaseApproved

First Approval Date

EU (19 Sep 1996),

Hepatitis AHepatitis B

Regulation-

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Structure/Sequence

Sequence Code 160473134

Author: Muratova, Olga ; Fintzi, Jonathan ; Samake, Yacouba ; Gorres, J Patrick ; Doumbo, Ogobara K ; Healy, Sara A ; Hume, Jen C C ; Imeru, Alemush ; Mohan, Rathy ; Kone, Mamady ; Duffy, Patrick E ; Doucoure, M'Bouye ; Sylla, Daman ; Kwan, Jennifer L ; MacDonald, Nicholas J ; O'Connell, Elise M ; Thera, Ismaila ; Sagara, Issaka ; Salazar-Miralles, Fernando ; Niaré, Karamoko ; Diarra, Balla ; Jones, David S ; Sissoko, Kourane ; Narum, David L ; Rausch, Kelly M ; Zaidi, Irfan ; Duan, Junhui ; Swihart, Bruce J ; Zhu, Daming ; Assadou, Mahamadoun H ; Morrison, Robert D ; Traore, Sekou F ; Coulibaly, Mamadou B ; Kamate, Bourama ; Neal, Jillian ; Guindo, Merepen A ; Anderson, Charles F ; Wu, Yimin ; Dolo, Amagana

BACKGROUNDMalaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians.METHODSWe did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462.FINDINGSBetween March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001).INTERPRETATIONPfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness.FUNDINGIntramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health.

30 Nov 2022·Human Vaccines & Immunotherapeutics

Modeling long-term persistence after 8 years of hepatitis B booster vaccination in 5- to 15-year-old children

Article

Author: Qiu, Yan ; Shen, Ling-Zhi ; Sun, Yu-Jing ; Liu, Ying ; Ren, Jing-Jing ; Wu, Jie ; Wu, Zi-Kang ; Yao, Jun ; Ren, Wen

Vaccination remains the most effective and cost-saving measure to protect against hepatitis B, a global health problem. It is crucial to characterize the persistence of the immune response after booster vaccination. This study aimed to quantify the persistence through mathematical modeling. Booster vaccination against hepatitis B was conducted in children 5-15 years in 2009-10 in Zhejiang Province. There were four dosage formulations of hepatitis B vaccines [Shenzhenkangtai Biotechnology Co. Ltd. Dalianhanxin Biotechnology Co. Ltd. NCPC GeneTech Biotechnology Pharmaceutical Co. Ltd. Sinovac Biotech Co. LTD. China]: 5, 10, and 20 μg hepatitis B vaccines or 5 μg hepatitis A and B (HAB) combination vaccine with a 0-1-6-month schedule. These were randomly administered to children negative for all hepatitis B markers, named as the schedule 2 group. Anti-HBs positive subjects were given one dose of booster, named as the schedule 1 group. Anti-HBs antibody was measured 1, 7, 18, 66, and 102 months after the first booster dose. A linear mixed-effects model was proposed to predict long-term persistence. One hundred two months after the booster dose, the mean anti-HBs levels were 33.8 mIU/mL, with 73.7 mIU/mL for the schedule 1 group and 20.2 mIU/mL for the schedule 2 group. The model predicted that 99.5% of subjects would remain seropositive (≥10mIU/mL) at year 20 post booster vaccination, with 100.0% and 98.8% for the schedule 1 group and the schedule 2 group, respectively, whereas at year 30, the seropositivity rates would decrease to 76.8%, with 99.4% for the schedule 1 group and 62.5% for the schedule 2 group. The immunogenicity of the booster vaccination could persist for at least 8 years. Mathematical modeling may predict even longer, up to 30 years of protection.

01 Dec 2020·Infectious Diseases and TherapyQ3 · MEDICINE

Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children

Q3 · MEDICINE

ArticleOA

Author: Badur, Selim ; Mitra, Monjori ; Ota, Martin O C ; Kolhapure, Shafi ; Agrawal, Ashish ; Andani, Anar ; Karkada, Naveen

INTRODUCTIONHepatitis A virus infection is more severe in adults than children. Although vaccination can protect adults, current childhood programs cover a large population more successfully. Childhood vaccination is, therefore, a solution to protecting adults if it induces lasting immunity. Fifteen-year protection has been demonstrated in children, but longer-term data are only available for adults. We aimed to predict long term persistence of antibody in children beyond 15 years and assess if immunological mechanisms triggered by vaccination support longer-term protection.METHODSLong-term clinical studies using hepatitis A (HAV) or A/B vaccines (HAB) containing 720 or 1440 Enzyme-linked immunosorbent assay Units (EU) of hepatitis A virus antigen were identified. Duration of persistence of antibodies and possible protection was determined by descriptively comparing antibody geometric mean concentration (GMC) kinetics, as well as GMC (95% confidence interval) at 15 years post-vaccination across studies. Immunological mechanism studies describing hepatitis A vaccination were identified.RESULTSOne study in children 12-15 years (2-dose HAB 720) and four in adults (2-dose HAV 1440 and 3-dose HAB 720) showed comparable GMC kinetics and per year rates of change up to 15 years. At 15 years, the GMC in children [414.7 mEU/ml (336.9; 510.5)] was in the same range as in adults [range 282.6 (217.6; 367.0) to 550.1 (416.0; 727.4)]. Based on these data, mathematical model predictions from adult studies (showing > 85% protected at 50 years) were deemed likely to also apply to children. Studies identified, both humoral and cell-mediated responses are induced following vaccination.CONCLUSIONBased on comparable antibody data in adults and children up to 15 years, similar longer-term antibody persistence is expected in children with 2-dose inactivated hepatitis A 720 containing vaccine at least up to 50 years. Accordingly, improving routine childhood hepatitis A vaccination coverage could protect against more severe disease in adulthood. Fig. 1 Plain language summary TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT00875485, NCT01000324, NCT01037114, NCT00289757, NCT00291876.

100 Deals associated with Hepatitis A inactivated & hepatitis B (recombinant) vaccine(GlaxoSmithKline Plc)

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis A	LI	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis A	EU	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis A	NO	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis A	IS	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis B	LI	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis B	NO	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis B	EU	GlaxoSmithKline Biologicals SA	19 Sep 1996
Hepatitis B	IS	GlaxoSmithKline Biologicals SA	19 Sep 1996

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis A	Discovery	AU	GSK Plc	01 Sep 2003
Hepatitis B	Discovery	AU	GSK Plc	01 Sep 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00289731 (CTgov)	Phase 4	Hepatitis A \| Hepatitis B	596	TWINRIX™ (Twinrix Group)	qlldggmdlt(cvkaadpotg) = cvetkxqixy wsgiuzrecs (xewdrvncrc, nzauhuwklk - frwppirbwf) View more	-	03 Oct 2018
				Engerix™-B+HAVRIX™ (Engerix-B+Havrix Group)	vipjberooc(twiisskqzr) = pnrpgtoevs uessyxtbwx (dgoegsoeyi, sscmyodmuy - ynoygboofx) View more
NCT01453348 (CTgov)	Phase 3	Hepatitis A \| Hepatitis B \| Meningitis, Meningococcal	252	HepA/B+MenACWY-CRM (HepA/B+MenACWY-CRM)	ejkpprzvmg(mpuvbfanpa) = bdwnqjtezj pjalhlknug (lyvlikwkdb, uwjtpuuokr - jqlatdzrve) View more	-	10 Mar 2014
				monovalent hepatitis A vaccine+hepatitis B vaccine+hepatitis A/B vaccine (HepA/B)	ejkpprzvmg(mpuvbfanpa) = quusndauba pjalhlknug (lyvlikwkdb, rcndvsyajf - detvyqelbl) View more
NCT00106964 (CTgov)	Phase 4	Hepatitis B \| HIV Infections	371	Hepatitis B vaccine (1: Engerix 20 mcg)	muvgnzblnt(cbdqclssyu) = wxxtfvqkib zvbepoxgwf (lqjvoiswqz, qlssxtpbfu - qpgcxnyvya) View more	-	28 Jun 2013
				Hepatitis B vaccine (2: Engerix 40 mcg)	muvgnzblnt(cbdqclssyu) = cnsqumauye zvbepoxgwf (lqjvoiswqz, kjuctkwkhf - rgjfwuvicl) View more
NCT00465816 (CTgov)	Phase 3	Meningococcal Infections	611	Nimenrix (Meningococcal vaccine 134612)+Twinrix (Nimenrix + Twinrix Group)	dkopxoekkh(bvlgppmtxd) = uxbdnwjlor cutyqxikud (gewefrmqdm, eqoqimozrw - wiwfglfkqf) View more	-	22 May 2012
				Nimenrix (Meningococcal vaccine 134612) (Nimenrix Group)	dkopxoekkh(bvlgppmtxd) = kcyzbxtind cutyqxikud (gewefrmqdm, zzlxpfojds - lmpmqehmdm) View more
NCT00289770 (CTgov)	Phase 3	Hepatitis A \| Hepatitis B	50	Twinrix	eckawymrgd(ucvjiocpff) = lzibnwvygz sybbqgvuee (afupuetsnb, toabqhexom - iaweoaiird) View more	-	23 Feb 2011
NCT00289718 (CTgov)	Phase 3	Hepatitis A \| Hepatitis B	51	Twinrix™ adult (Twinrix Group)	rplfnygeju(ddktbsgrid) = ktgxydqylt ohdwrvrkku (ipqvnoskvs, hjtulkfzzr - oarhczkqpj) View more	-	26 Aug 2010
				Twinrix™ adult (TWINRIX GROUP)	tyrpwlvovk(rmbembiegb) = afwyiqcpzh utkvwkvmqd (ycbavvbaqu, kcmlquauwz - mjkysiiciy) View more
NCT00289744 (CTgov)	Phase 3	Hepatitis A \| Hepatitis B	178	TWINRIX™ ADULT (Twinrix Group)	emkojfovyk(lollptiuzh) = uyzzfcixyk igshqkflxw (qdwlppjpaj, bgwylroywz - xasbwgmpnp) View more	-	26 Aug 2010
				Engerix TM (Engerix-B Additional Dose (Adult))	crckcbnufx(vnkbbjxvrl) = kxlzvkcwvj cfdiudswwe (mkfcdnncpd, lllvftsdqd - klmoaukieh) View more
NCT00578227 (CTgov)	Phase 3	Human Papillomavirus Infection	814	Cervarix™+Twinrix ™ Paediatric (Cervarix™ & Twinrix™ Group)	zvqwvvfjeq(phxhhxfoiu) = zkkudnzopa mthuawgyav (jnsfvbiqbr, dsklcbkvij - eeghtggbao) View more	-	06 Jan 2010
				Cervarix™ (Cervarix™ Group)	ggvofvswyl(ceqlsrqqqm) = dcpbvwikef ikmbvjmvee (xejkxwjmuj, erifotmmmd - vlzxdbwkah) View more
NCT00684671 (CTgov)	Phase 4	Hepatitis A \| Hepatitis B	506	Twinrix (Twinrix Group)	uiwwvzezgd(rihvfgawwo) = rxaovaelfa mtfxtjrqgx (roggmqhvll, mevjruymgb - bwhphyahjd) View more	-	03 Dec 2009
				Engerix-B+Havrix (Engerix + Havrix Group)	uiwwvzezgd(rihvfgawwo) = ttskbabqiu mtfxtjrqgx (roggmqhvll, ruqqjizpss - uiwfwtdejv) View more
NCT00197119 (CTgov)	Phase 3	Hepatitis A \| Hepatitis B	244	Twinrix™ Junior (Group Twinrix Junior)	zeevvguqts(huefmeewiy) = iybcjepwoc nkwdrpfenk (gynbciitps, odepiiakof - cakhebcngs) View more	-	14 Aug 2009
				Twinrix™ Adult (Group Twinrix Adult)	zeevvguqts(huefmeewiy) = rqqqzwfrar nkwdrpfenk (gynbciitps, vgzgsavjxq - bsqdfctegk) View more