Rotavirus Strain Surveillance in the Vaccine Era: Why should we - - PowerPoint PPT Presentation

▶
rotavirus strain surveillance in the vaccine era why
SMART_READER_LITE
LIVE PREVIEW

Rotavirus Strain Surveillance in the Vaccine Era: Why should we - - PowerPoint PPT Presentation

Jan 16, 2023 7 likes •213 views

Rotavirus Strain Surveillance in the Vaccine Era: Why should we characterize strains? Jon Gentsch, Carl Kirkwood, George Armah, Jim Gray, Miren Iturriza-Gomara, Nicola Page, Duncan Steele, Mathew Esona, May El Sherif and Roger Glass Centers

slide-1
SLIDE 1

Rotavirus Strain Surveillance in the Vaccine Era: Why should we characterize strains?

Jon Gentsch, Carl Kirkwood, George Armah, Jim Gray, Miren Iturriza-Gomara, Nicola Page, Duncan Steele, Mathew Esona, May El Sherif and Roger Glass

Centers for Disease Control and Prevention, Atlanta, USA; Murdoch Childrens Research Institute, Melbourne, Australia; NMIMR, University

  • f Ghana, Legon; Health Protection Agency,

London, United Kingdom; Medical University of South Africa, Pretoria, South Africa

slide-2
SLIDE 2

Importance of Rotavirus Strain Surveillance and Molecular Epidemiology

Vaccine Research

  • serotypes of vaccines
  • impact of vaccine on strains
  • reassortment of vaccine in vivo

Virus Evolution

  • origin of new strains
  • animal rotavirus role
  • reassortment between strains
  • genetic variation in RV genes
slide-3
SLIDE 3

Rotavirus Surveillance Studies

  • Lessons learned in pre-vaccine era
  • Goals of surveillance during vaccine

program implementation

  • Reference lab activities supporting

surveillance programs

slide-4
SLIDE 4

Rotavirus Structure

RNA Segment Protein 1 2 3 4 5 6 7 8 9 10 11 VP1 VP2 VP3 VP4 NSP1 VP6 NSP2 NSP3 VP7 NSP4 NSP5

VP2 VP4 Neutralization antigen VP6 Subgroup antigen VP7 Neutralization antigen Subcore

slide-5
SLIDE 5

P[8]G4 7.5%

P[8]G1 52.2%

  • ther

18.2% P[8]G3 2.8% P[4]G2 11.5%

Lessons from Surveillance: 1. Limited Number of Globally Common Strains

N=21,256 (1993-2003) Gentsch et al, JID, 2005 Rare or regionally common strains (25 strains total): P[4]G1 (1.3%), P[6]G2 (0.8%), P[6]G1 (0.6%), P[6]G8 (0.6%), P[4], G3 (0.5%)

5.5%

slide-6
SLIDE 6

Lessons from Surveillance: 2. Large Variation in Strain Incidence between Developed and Developing Regions

P[6]G1 or G2 4% P[6]G2 10% P[8]G1 19%

  • ther

28% P[8]G4 2% P[8]G3 8% P[4]G2 3% P[8]G9 6% P[6]G8 10% P[8]G9 1% P[4]G1 1%

  • ther

15% P[8]G4 12% P[8]G3 2% P[4]G2 9% P[8]G1 60%

Europe Africa

N=6328 Gentsch et al, JID, 2005 N=1147

slide-7
SLIDE 7

6[1]

US585 12 Mc35 I321 10 Mc323 116E US120 5 WI61 9 HAL116 6 69M MW023 MW333 8 PA169 PA151 6 Br1054 5 ST-3 Hochi 4 157C HCR3 AU-1 McN13 107E1B P 3 1076 DS-1 2 K8 AU19 M37 AU64 Wa 1

12[19] 11[14] 8[11] 5A[3] 4[10] 3[9] 2C[6] 2A[6] 1B[4] 1A[8] G type

Lessons from Surveillance: 3. Extensive Serotype Diversity and Reassortment

P serotype [genotype] Globally Common Uncommon Regionally Common Neonates

Gentsch et al, JID, 2005

slide-8
SLIDE 8

Genotypic Properties (gene segment): G type P type (4) Subgroup (6) PAGE pattern (11) No of strains 9 8 II Long 1 9 6 I Short 32 9 6 I, II Long 5 9 8 I Short 9 9 ND Short 6 9 ND Long 3

Distribution of natural RV G9 reassortants in Bangladesh

Unicomb, et al. 1999

Reassortment in Multiple Gene Segments

slide-9
SLIDE 9

Lessons from Surveillance: 4. Emergence of Serotype G9 (1995-2005)

First reports, mid 1980s G9 reports - late 1980s through 2005 Philadelphia, 83 Osaka, 85

slide-10
SLIDE 10

Surveillance goals during and after implementation of vaccine programs?

  • Breakthrough strains that appear after

vaccination

  • Changes in serotype incidence and the

emergence of novel strains with distinct G and P serotypes

  • Circulation of vaccine strains in children
  • Reassortment with wild-type human

rotaviruses, yielding new strains or changes in virulence

slide-11
SLIDE 11

What kind of breakthrough strains might

  • ccur after Vaccination with Rotarix and

Rotateq?

G1P1A[8]

G1 G3 G2 G4 P1A[8]

Human rotavirus Bovine rotavirus with single human rotavirus gene substitution

GSK Bio (Rotarix) Merck (Rotateq)

slide-12
SLIDE 12

High High P[8], G4 High High P[8], G9 High Reduced P[4], G2 High High P[8], G3 High High P[8], G1 Rotateq** (P[8], G1-G4) Rotarix (P[8]G1) Infecting strain Efficacy

**Only G types of infecting strains reported Adapted from Vesikari et al and Ruiz-Palacios et al, N Engl J Med: 354, 2006

Efficacy of Licensed Rotavirus Vaccines

slide-13
SLIDE 13

Other Strains with Reduced Efficacy or Failure?

1 11 10 9 8 7 6 5 4 3 2 11 10 9 8 7 6 5 4 3 2 P[8]G1 P[8]G3 P[8]G4 P[8]G9

P[4]G2 P[6]G9 Rotarix

VP4 (P) VP6 VP7 (G) NSP4

P[8]G1

High efficacy Reduced Efficacy Wa genogroup DS-1 genogroup Within genogroups - high genetic homology and antigenic relatedness Between genogroups – lower genetic homology and antigenic relatedness Efficacy?

P[6]G12

slide-14
SLIDE 14

Potential Breakthrough Strains with Rotateq

P[6]G9 P[6]G12

Wa HRV genogroup DS-1 HRV genogroup AU-1 HRV genogroup

P[8] G1 G2 G3 G4

Bovine genogroup Strains from the United States

P[9]G6

slide-15
SLIDE 15

Circulation of Vaccine Strains and Reassortment with HRV

  • Rotarix – expect reassortment with natural

RV (P[8]G1, P[8]G9,etc) during mixed infections

– Reassortment in all 11 genes likely

  • Rotateq?
  • Potential to produce new strains with

altered virulence – important surveillance issue

slide-16
SLIDE 16

1 2 3 4 5 6 7 8 9 10 11

Genogroup Specificity

Wa DS1

Segments

High Throughput Techniques are needed To Study Reassortment in all Genes: Gene Segment Typing by Microarray

a b c d e f g h i j

Wa Wa DS1 DS1

B223/Bov

Strain 116e P[8]G1 P[4]G2 Strain 116e P[8]G1 P[4]G2 Strain 116e B223/Bov

V P 4 V P 7 B223/Bov NS NS

slide-17
SLIDE 17

Rotavirus Reference Centers and Collaborating Centers

  • Supported by WHO and PATH
  • Set up to support surveillance networks
  • Provide training, protocols, reagents and

assistance

  • Prepared a unified lab manual of rotavirus

characterization protocols

slide-18
SLIDE 18

Rotavirus Reference Centers and Collaborating Centers

WHO Collaborating Center CDC, Atlanta WHO Collaborating Center Murdoch Childrens Research Institute Melbourne South African Reference Center MEDUNSA Pretoria West African Reference Center NMIMR, Univ. of Ghana Legon United Kingdom Reference Center Health Protection Agency London

slide-19
SLIDE 19

MANUAL OF ROTAVIRUS CHARACTERIZATION METHODS Draft Version

This document was produced by the Laboratory Directors of the European, West African, and South African Rotavirus Reference Laboratories, and the WHO Rotavirus Collaborating Centers in Melbourne, Australia, and Atlanta, Georgia, United States

Copies may be requested from:

Jim Gray Health Protection Agency London, United Kingdom Jim.Gray@HPA.org.uk George Armah West African Reference Center NMIMR, Univ. of Ghana Legon GArmah@noguchi.mimcom.net Nicola Page South African Reference Center MEDUNSA Pretoria pagenic@medunsa.ac.za Carl Kirkwood WHO Collaborating Center Murdoch Childrens Research Institute Melbourne carl.kirkwood@mcri.edu.au Jon Gentsch WHO Collaborating Center CDC, Atlanta jgentsch@cdc.gov

slide-20
SLIDE 20

Summary

  • Rotavirus strain surveillance and

characterization studies have played key role in defining serotypes important for vaccines and understanding strain diversity and mechanisms of evolution

  • During and after vaccine programs are

implemented surveillance will be crucial to monitor changes in serotypes and vaccine effectiveness