Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines

Figures & data

Table 1. Overview of oral, live-attenuated rotavirus vaccines pre-qualified by the World Health Organization as of Jan 2020

Vaccine	Manufacturer	Composition	Dosage	Formulation	Storage^a	EPI schedule	WHO pre-qualification^a
RotaTeq	Merck & Co., Inc.	Pentavalent human-bovine mono-reassortants: human G1, G2, G3, G4, P[8] on bovine rotavirus (WC3) backbone	2–2.8 x 10^6 IU/serotype	Liquid	2–8  C, 24 mo	6, 10, 14 weeks	Oct 2008
Rotarix	GlaxoSmithKline Biologicals	Monovalent G1P[8] (strain RIX4414) human rotavirus	≥10^6 CCID50	Liquid	2–8  C, 24 mo	6, 10 weeks	Mar 2009
Rotavac^b	Bharat Biotech International Ltd.	Monovalent G9P[11] (strain 116E) natural human-bovine reassortant	≥10^5 FFU	Liquid	−20 C, 60 mo After thaw: 2–8 C, 6 mo	6, 10, 14 weeks	Jan 2018
Rotasiil^c	Serum Institute of India Pvt. Ltd.	Pentavalent human-bovine mono-reassortants (BRV-PV): human G1, G2, G3, G4, G9 on bovine rotavirus (UK) backbone	≥10^5^.^6 FFU/serotype	Lyophilized	2–8 C, 30 mo	6, 10, 14 weeks	Sep 2018
Rotasiil Thermo	Same	Same	Same	Lyophilized	25 C, 30 mo	Same	Jan 2020

Abbreviations: CCID₅₀, cell culture infective dose 50; EPI, Expanded Programme on Immunizations; IU, international units; FFU, focus-forming units; WHO, World Health Organization

a. Ref¹⁸

b. Rotavac 5D: storage at 2–8 C but not yet pre-qualified by WHO

c. Rotasiil: liquid formulation requiring storage at 2–8 C not yet pre-qualified by WHO

Table 2. Summary of recent oral rotavirus vaccine effectiveness studies in LMIC

				Adjusted vaccine effectiveness (95% CI)
Country	Vaccine	Setting	Age (years)	Any rotavirus gastroenteritis	Severe rotavirus gastroenteritis	Ref
Bangladesh	Rotarix	Hospital, Outpatient	<2	41% (23–55)	43% (22–58)	^Citation27
Burkino Faso	RotaTeq	Hospital	<5 6–11	35% (−15-63) 58% (10–81)	39% (−18-68) NR	^Citation28
Lebanon	Rotarix, RotaTeq	Hospital	<5	68% (50–80)	NR	^Citation29
Malawi	Rotarix	Hospital	<5	62% (28–80)	75% (41–89)	^Citation30
			<12 mo	75% (45–89)	83% (54–94)
Philippines	Rotarix	Hospital	<5	62% (26–80)	67% (18–87)	^Citation31
Tanzania	Rotarix	Hospital	<2	49% (−30-80)	66% (−2-89)	^Citation32
Tanzania	Rotarix	Hospital	<5	75% (−8-94)	NR	^Citation33
				85% (27–97)^a	NR
Thailand	Rotarix	Hospital	<18 mo	88% (76–94)^b	NR	^Citation34
Zimbabwe	Rotarix	Hospital, ED	1–5	−48% (−148-11)	−38% (−164-28)	^Citation35
			6–11 mo	61% (21–81)	68% (13–88)

Rotavirus detection by stool rotavirus enzyme immunoassay except as otherwise noted.

Abbreviations: NR, not reported

^aDetection by qPCR

^bDetection by polyacrylamide gel electrophoresis

Table 3. Overview of newer and next-generation vaccines under evaluation or in development

Vaccine type	Manufacturer/Developer	Composition	Status
Oral, live-attenuated
RV3-BB	PT BioFarma	Monovalent G3P[6] (strain RV3) neonatal human rotavirus	Phase 2/3
Non-replicating, parenteral
P2-VP8*	PATH SK Bioscience	Trivalent subunit vaccine: tetanus toxoid P2 fused to P[4] (strain DS1), P[6] (strain 1076), and P[8] (strain Wa) VP8*	Phase 3
CDC-9	CDC Serum Institute of India Pvt. Ltd Zhifei Lvzhu Biopharmaceutical Co., Ltd.	Monovalent inactivated human rotavirus strain CDC-9	Preclinical
116E	Bharat Biotech International Ltd.	Monovalent inactivated human rotavirus strain 116E	Preclinical
VLP VP2/6/7	Mitsubishi/Medicago	Virus-like particle	Phase 1
VLP VP2/4/6/7	Baylor College of Medicine	Virus-like particle	Preclinical
VP6 + norovirus	Tampere University, Finland	Nanoparticle: VP6 nanotubes or microspheres + norovirus viral-like protein admixture	Preclinical
VP6 + norovirus	Cincinnati Children’s Hospital Medical Center	Sub-viral particles (norovirus S or P) expressing rotavirus VP8* particle	Preclinical
VP8* mRNA	CureVac	VP8* mRNA	Preclinical

Newer formulations of already licensed vaccines are not included.

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