Rotavirus Vaccines

1
Rotavirus Vaccines

• Duncan Steele1 and Robin Biellik2
• 1Initiative for Vaccine Research, IVB, WHO,
  Geneva
• 2Rotavirus Vaccine Programme, PATH, Seattle

Eastern Southern African GAVI Regional Working
Group 4-5 October 2005 Harare, Zimbabwe
2
Rotavirus Disease Burden

• Rotavirus is the most common diarrhoeal pathogen
  in children worldwide1
• Globally gt 125 million cases of infantile
  gastro-enteritis2
• 500,000 deaths per year
• 85 in less developed countries3

Estimated global distribution of 440,000 annual
deaths in children lt5 years old caused by
rotavirus diarrhea3 1 dot 1000 deaths
1Parashar et al, Emerg Infect Dis 1998 4(4)
561570 2Linhares and Bresee, Pan Am J Public
Health 2000 8(5) 305331 3Parashar et al, Emerg
Infect Dis 2003 9(5) 565572
3
Rotavirus Epidemiology

• Rotavirus is ubiquitous - 95 of children
  worldwide infected by 13y of age1
• Peak incidence of clinical illness among children
  aged 618 months
• The younger the child, the higher the risk of
  severe disease, hospitalization or death2
• Rotavirus accounts for approximately one third of
  cases of severe vomiting and diarrhoea requiring
  hospitalization1

1Parashar et al, Emerg Infect Dis 1998 4(4)
5615702Linhares and Bresee, Pan Amer J Public
Health 2000 8(5) 305330
4
Burden of Rotavirus Disease Studies in Africa

• Guinea Bissau1
• 3.4 rotavirus deaths / 1000 infants per year
• 145 000 rotavirus-related deaths in Africa
• Sub-Saharan Africa2
• 110-155 000 rotavirus-related deaths per year
• Country-specific mortality3,4
• Nigeria 80-90 deaths per day
• Cameroon 50-60 deaths per day
• South Africa 10-12 deaths per day

1Mølbak et al, Vaccine 2000 19 393-395 2Miller
McCann, Health Econ 2000 9 19-35 3Parashar et
al, Emerg Infect Dis 2003 4Steele et al,
Vaccine 2003 21(1) 354-360 Afr Health Sc J 2002
9(4) 103-107
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Epidemiology of Rotavirus in Africa

• Rotavirus infection occurs in 25-40 of children
  hospitalized with diarrhoeal illness
• More common in hospitalized children than in
  outpatients
• Rotavirus disease occurred in
• 17 of infants less than 6 months of age
• 75 of infants less than 12 months of age
• 83 of children under 18 months of age
• Seasonal distribution with peak in cool, dry
  months

Cunliffe et al, Bull WHO 1998 76(5)
525-537 Steele et al, Vaccine 2003 21(1) 354-360
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Rotavirus Surveillance Networks
EMRO
Asia
South
Asia
South
America
Africa
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Rotavirus Surveillance in Africa

• Co-ordinate rotavirus surveillance activities in
  AFRO
• First meeting was held in Ghana, May 2005
• Co-ordinator to be appointed in AFRO, Harare
• Proposals received for 4-5 countries' MOH for
  routine surveillance for rotavirus, others
  anticipated
• Linked with existing networks (eg. PBM, measles
  etc)
• Subsidised ELISA kits have been negotiated by
  WHO/CDC will be purchased and distributed by
  AFRO
• Regional Reference Laboratories established to
  support training and support activities of AFRO

8
Rotavirus Vaccine Candidates

• Licensed Rotavirus Vaccines
• RotaShield - licensed by FDA, remains in place
  and efforts being made to produce the vaccine
  again
• Lanzhou Lamb RV (LLR) licensed in China and
  used in private market
• Rotavirus Vaccines of Interest
• Rotarix (GSK) - licensed in Mexico 14 others
• RotaTeq (Merck) - phase III clinical trials

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RotaShield Clinical Efficacy
US Multi Finland Venezuela

100
100
100
97
100
80
75
73
70
71
69
60
40
20
0
MD visits orillness gt4 days
Dehydration
Hospital admittance
Rennels et al Pediatrics 1996977-13. Santosham
et al J Pediatr 1997131632-638. Joensuu et al
Lancet 19973501205-1209. Pérez-Schael et al N
Engl J Med 19973371181-87
10
Rotarix (GSK Biologicals)
Glaxo SmithKline (GSK)
Manufacturer
Human, monovalent rotavirus
Origin
Lyophilised, reconstituted
Presentation
Oral, by applicator
Administration
2-8oC
Storage
2 doses
Dosage
None with OPV, DTPa, DTPw, HepB, Hib, pneumo
Vaccine interference
11
Rotarix (GSK Biologicals)
Evaluated in Latin America (n11) and
Finland gt63,000 infants 6-14 weeks of age
followed for safety against intussusception No
reported association with intussusception 20,000
infants followed for efficacy Efficacy against
any rotavirus GE 65 severe
rotavirus GE 77
Rotavirus immunogenicity trials completed in
South Africa. Safety in HIV infants
ongoing. Rotavirus efficacy studies planned in
South Africa (2005) and Malawi (2006)
Vesikari, ESPID, Valencia, 2005Velasquez, ESPID,
Valencia, 2005
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Current Status of Rotarix

• Licensure of Rotarix
• First licensed in Mexico in July 2004
• Now licensed in another 14 countries
• gt40 national submissions worldwide
• Already licensed in Kenya, Malawi, Mauritius
• License submitted to EMEA expected in 1Q06
• Enable GSK to apply for pre-qualification
• Already utilised in the private markets in
  Mexico, Peru etc
• Brazil MOH intends to include in routine
  immunization programme by end of 2005

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RotaTeq (Merck)
Merck Research Laboratories
Manufacturer
Bovine-Human rotavirus reassortant, pentavalent
Origin
Liquid
Presentation
Oral, squeeze tube
Administration
2-8oC
Storage
3 doses
Dosage
None with IPV, DTPa, DTPw, HepB, Hib, pneumo
Vaccine interference
14
RotaTeq (Merck)
Evaluated in United States, Europe (n5) and
Latin America (n5) gt72,000 infants 6-14 weeks of
age followed for safety against
intussusception No reported association with
intussusception 5,000 infants followed for
efficacy (US and EU) Efficacy against any
rotavirus GE 74 severe rotavirus
GE 98
Vesikari, ESPID, Valencia, 2005Dennehy, ESPID,
Valencia, 2005
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Current status of RotaTeq

• Licensure
• Dossier submitted to FDA and EMEA
• Expected approvals in early 2006
• Clinical trials are being planned in Africa and
  Asia
• Protocols available
• Country and selection

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Rotavirus vaccines are no longer vaccines of the
future, but will be used in routine EPI schedules
in other regions within the next year
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African Rotavirus Studies1998 - 2003

• Lab based studies
• Epidemiology
• Strain Surveillance

Laboratories or hospitals doing diarrhoeal
research
Steele et al, Vaccine 2003 21(1) 354-360