Product review of the rotavirus vaccines ROTASIIL, ROTAVAC, and Rotavin-M1

Figures & data

Table 1. Product characteristics of Rotavin-M1, ROTAVAC, and ROTASIIL ^{(9, 47, 48, 50, 93−96).}

Vaccine	Rotavin-M1	ROTAVAC	ROTASIIL
Manufacturer	Polyvac; Center for Research and Production of Vaccines	Bharat Biotech	Serum Institute of India
Dose schedule	2-dose (first dose from 6 weeks, second dose from 1–2 months; should be given before 6 months of age)	3-dose (with DTP 1, 2, and 3)	3-dose (with DTP 1, 2, and 3)
Dose volume	2.0 mL	0.5 mL	2.5 mL
Doses per container	1	5, 10	1, 2
Strains	Single, attenuated human rotavirus strain (G1P[8])	Single, attenuated human rotavirus strain (G9P[11])	5 human-bovine (UK) reassortant rotaviruses (G1, G2, G3, G4, G9)
Presentation	Liquid vaccine in glass vial	Liquid in glass vial	Lyophilized in glass vial; antacid diluent from separate vial used to reconstitute
Storage	Frozen (−20-5°C)	Refrigerated (2–8°C): 6 months Frozen (−20°C): 5 y*	Vaccine -Refrigerated (2–8°C): 30 months Diluent – Ambient temperature of refrigerated (2–8°C): 60 months†
Cold storage volume per course	Not publicly available	1-dose: 45 cm^3 5-dose:12.6 cm^3 10-dose: 9.6 cm^3	1-dose: 53 cm^3 2-dose: 32 cm^3 ‡
Vaccine vial monitor	No	Yes (VVM2)	Yes (VVM30)
Route of administration	Oral	Oral	Oral
UNICEF price per course (Gavi-supported countries, 2020) §	n/a	5- and 10-dose vials: 2.55 USD	1-dose vial: 4.65 USD 2-dose vial: 2.85 USD

*Can be frozen-thawed 6 times without losing potency

†Once reconstituted, can be refrigerated (2–8°C) for up to 6 hours

‡ Cold storage volume excludes diluent

§ USD, does not consider wastage

Table 2. Summary of clinical trials for Rotavin-M1, ROTAVAC, and ROTASIIL

Rotavin-M1
Study	Phase	Date	Design	Participants	Primary Objective
NCT01375907^Citation55 Dang, 2012^Citation44	I	Started: 2009 Completed: 2009	Single group assignment to experimental group	160 healthy adults	Evaluate safety
NCT01377571^Citation56 Dang, 2012^Citation44	II	Started: 2009 Completed: 2010	Randomized parallel assignment to four experimental arms (varying dose schedule)	160 healthy infants (6–12 weeks at enrollment)	Evaluate safety and immunogenicity
NCT01502969^Citation57	II/III	Started: 2010 Completed: 2011	Randomized parallel assignment to two arms (placebo or experimental)	799 healthy infants (6–12 weeks at enrollment)	Evaluate safety and immunogenicity
NCT03703336^Citation46	III	Started: 2019 Still in progress	Randomized parallel assignment to two arms (frozen formulation or liquid formulation)	825 healthy infants (60–91 d at enrollment)	Demonstrate non-inferiority in the immunogenicity of the liquid formulation compared to the frozen formulation
ROTAVAC
Study	Phase		Design	Participants	Primary Objective
Bhandari, 2006^Citation58	I/II	Started: 2005 Completed: 2005	Double-blind, randomized, controlled trial	369 healthy infants	Evaluate safety and immunogenicity
Bhandari, 2009^Citation59	I/II	Started: 2006 Completed: 2008	Double-blind, placebo controlled, dose-escalation trial	187 health infants (6 weeks at enrollment)	Evaluate safety
Appaiahgari, 2014^Citation60	I/II	Started 2006 Completed: 2008	Randomized, double-blind, placebo-controlled	369 healthy infants (6 week at enrollment)	Dose escalation safety and immunogenicity
NCT03602053^Citation61	II	Started: 2018 Completed: 2019	Single center, randomized, controlled, open label study	450 healthy infants (6–8 weeks at enrollment)	Compare immunogenicity, reactogenicity, and safety of frozen and liquid formulations
NCT01305109^Citation62 Bhandari, 2014^Citation29 Bhandari, 2014^Citation63	III	Started: 2011 Completed: 2014	Randomized, double-blind, placebo-controlled trial (placebo or experimental)	6799 healthy infants (6–7 weeks at enrollment)	Evaluate efficacy
NCT03367559^Citation64	III	Started: 2018 Completed: 2019	Open-label, single group assignment	360 healthy infants (6–8 weeks at enrollment)	Immunogenicity, safety, and reactogenicity
Chandola, 2017^Citation65	III	Started: 2014 Completed: 2015	Randomized, double-blind, placebo-controlled	1356 healthy infants (6 weeks at enrollment)	Effect of vaccine on other co-administered childhood vaccines
Praharaj, 2019^Citation66	III	Started: 2018 Completed: 2018	Double-blind, placebo-controlled	1169 healthy infants (6–8 weeks at enrollment)	Impact of coinfections on efficacy estimates
Ella, 2018^Citation67	IV	Started: 2014 Completed: 2014	Randomized, single-blind	900 healthy infants (6–8 weeks at enrollment)	Immunogenicity, reactogenicity, and safety when administered with or without buffering agent
Ella, 2019^Citation68	IV	Started: 2015 Completed: 2016	Open-label, randomized assignment (two experimental groups with different doses)	464 healthy infants (6–8 weeks at enrollment)	Antibody response of two different dosing schedules
ROTASIIL
Study	Phase	Date	Design	Participants	Primary Objective
Zade, 2014^Citation69	I/II	Started: 2014 Completed: 2014	Randomized, double-blind, placebo controlled	60 healthy infants	Evaluate safety and immunogenicity
NCT03474055^Citation70 Kawade, 2019^Citation53	II/III	Started: 2017 Completed: 2018	Randomized parallel assignment to four experimental arms (three liquid and one lyophilized)	1500 healthy infants (6–8 weeks at enrollment)	Compare liquid formulation to lyophilized formulation.
NCT02133690^Citation71 Kulkarni, 2017^Citation30	III	Started: 2014 Completed: 2017	Randomized parallel assignment to two arms (placebo or experimental)	7500 healthy infants (6–8 weeks at enrollment)	Evaluate efficacy
NCT02145000^Citation72 Isanaka, 2017^Citation73 Coldiron, 2018^Citation74	III	Started: 2014 Completed: 2019	Randomized parallel assignment to two arms (placebo or experimental)	4092 healthy children (6 weeks to 2 years at enrollment)	Evaluate efficacy and safety
NCT02584816^Citation75 Desai, 2018^Citation76	III	Started: 2015 Completed: 2017	Randomized parallel assignment to four arms (three experimental and one active comparator)	1500 healthy infants (9–8 weeks at enrollment)	Evaluate lot-to-lot consistency in manufacturing

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