Vaksienes: opgedateerde weergawe

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Vaksienes opgedateerde weergawe

• Dr Lynne Webber
• Maart 2008

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Lewende vaksienes en tyd

• Pokke
• Antraks
• Hondsdolheid
• BCG
• Geelkoors
• OPV
• Masels
• adenovirusse
• 1798
• 1881
• 1885
• 1927
• 1935
• 1962
• 1963
• 1971

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Lewende vaksienes en tyd

• Waterpokkies
• Rotavirus
• Duitse masels
• Lewende griep
• Onaktiewe griep
• Lewende griep
• Rotavirus koei-mens stam

• 1995
• 2005
• 1969
• 2003
• 1970s
• 2003
• 2005

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1950s The cell-culture revolution

• Mass production of virus followed by complete
  inactivation. Virus grown in
• Eggs (influenza type A B)
• Continuous monkey kidney cell lines
  (poliovirus 1,2 3) IPV (Salk)
• Human diploid fibroblasts (rabies,
  HAV)
• Mouse brain (JEV)

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1900s Viral subunit vaccines

• Virus is inactivated with a chemical such as
  formalin and/or disrupted with a detergent e.g.
  Influenza vaccines

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1986 Recombinant subunit vaccines

• Construction of inactivated antigens e.g.

• Hepatitis B vaccine manufactured in a yeast
  recombinant carrying the gene for the S protein
• Insertion of genes into yeast, Escherichia coli
  or Chinese hamster ovary cells enabled production
  of a variety of recombinant proteins in
  development
• Lyme OspA, cytomegalovirus gB, pertussis toxin

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2006 Recombinant subunit vaccines- Virus-like
particles (VLPs)

• Capsid proteins of nonenveloped viruses the
  nucleocapsid of some enveloped viruses can
  self-assemble into VLPs
• VLPs consist of capsid proteins assembled into a
  similar shell like structure, but viral nucleic
  acid is not present within the shell

• These shells can display conformational epitopes
  that are not present on individual purified
  capsid proteins

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Nie-lewende vaksienes

• Tifoied, cholera en plaag
• Heel-sel pertussis
• Griep
• IPV
• Hepatitis A
• Japanese enkefalities

• 1896 7
• 1926
• 1938
• 1955
• 1995
• 1944

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Nie-lewende vaksienes

• Meningokokaal
• Pneumokokaal
• Tifoied
• H. influenza b
• Staphylokokaal
• Hepatitis B
• Menslike papiloomvirus

• 1974
• 1977
• 1995
• 1987
• Future
• 1986
• 2006-2007

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Recombinant vector vaccines
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Replication-competent vectors (recombinant live
attenuated virus vaccines)

• Molecular technologies are used to construct
  viable recombinants

• Possess
• surface proteins of a virus against which the
  vaccine is directed plus
• the remaining coding noncoding regions of
  another related virus that bears attenuating
  mutations

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Immunology finally helps vaccinology

• Most successes in immunization have been mediated
  through the induction of protective antibodies
• Major challenge induction of T cell immunity
• Several of the new strategies, incl. vectors,
  plasmid DNA lipidated peptides, are capable of
  inducing both CD4 CD8 cellular responses
• Stimulation of innate adaptive immune responses
  can be accomplished by the choice of proper
  adjuvants
• Adjuvants for vaccines
• until recently essentially limited to aluminum
  salts (alum) that stimulate a T helper type 2
  (Th2) response
• creation of new oil-in-water emulsions,
  liposomes, Toll-like receptor (TLR) agonists,
  cytokines other substances that push the immune
  system in a T helper type 1 (Th1) direction

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Nuwe gedagtes!
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Enlargement of routes of immunization need for
mucosal immune responses

• Transdermal application deliver Ag across the
  skin
• Closest to actual use e.g. Hepatitis B, anthrax
• Many devices have been developed e.g.
• patches applied to lightly abraded skin
• microneedles to pierce the stratum corneum

• Once past the superficial layer the Ag comes in
  contact with DCs ? travel to LN initiate immune
  responses
• If transdermal immunization works well,
  vaccination practice could be revolutionized

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SA Childhood EPI schedule
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Recommended immunization schedule for ages 0 to 6
years, US 2007
http//www.cdc.gov/vaccines/recs/schedules/downloa
ds/child/2007/child-schedule-color-print.pdf
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HPV vaccines

• Gardasil (Merck) was FDA EU approved in 2006
• VLPs from HPV types 6, 11, 16 18 manufactured
  in a yeast system with alum as adjuvant
• Cervarix (GSK) are pending FDA approval
• VLPs from HPV types 16 18 manufactured in a
  baculovirus system
• Three-doses regimen 0-, 2-, 6-months
• Efficacy safety
• 99.7 of those vaccinated developed an Ab
  response
• In 16-23 year old ? HPV 16 naïve at baseline
  100 effective
• No serious vaccine-related adverse events

• CDC recommendations
• 11-26 year old females regardless of whether or
  not they have had prior gynaecological or Pap
  screening even with a history of having an
  abnormal Pap examination
• Ideal 9-15 years old before sexual debut
• NOT a therapeutic vaccine

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A vast array of vaccinations

• By the age of 18 children in the US will have
  received up to 44 vaccine injections
• Excl. rotavirus (oral) HPV

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New combination approaches

• Co delivery of multivalent vaccines
• Co delivery by different routes
• Sequential combination of vaccines
• (Prime-boost strategies)

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Co delivery of multivalent vaccines Combination
vaccines

• Hexavalent combinations (Hib/DTaP/IPV/HBV)
• used in Europe
• Pentavalent combinations (Hib/DTaP/IPV)
• used in many parts of the world
• Pentacel pending FDA licensure in the US
• Varicella vaccine has been incorporated into
  measles-mumps-rubella vaccines (MMR-V)
• ProQuad FDA licensure 2005

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New population target groups for vaccination
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Herpes zoster vaccine for prevention of zoster

• 2 new vaccine formulations have been evaluated
• Heat inactivated Oka/Merck vaccine preparation
  was associated with a reduced incidence of zoster
  to 13 during the first year after autologous
  hematopoeitic cell transplantation when given as
  1 dose before and 3 doses after transplantation
• Higher potency live attenuated Oka vaccines were
  developed evaluated for their potential to
  increase VZV cellular immunity in healthy older
  adults (gt60 years)
• Zostavax FDA licensed in 2006

• VZV-specific memory T cells decline with age
• The administration of zoster vaccine to older
  persons may prevent VZV-specific T cells from
  dropping below the threshold for zoster occurrence

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Dankie en sterkte vir die res van die dag!