Development of Vaccination Methods to Induce AntiHIV Mucosal Immunity

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Development of Vaccination Methods to Induce
Anti-HIV Mucosal Immunity
Herman F. Staats, Ph.D.
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• Rationale for Mucosal Immunization
• Adjuvants for Mucosally-Administered Vaccines
• Prime-Boost Immunization Methods
• Future Studies

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Rationale for Mucosal Immunization

• Induction of mucosal and systemic immune
  responses
• S-IgA, IgG, CD4 , CD8
• Mucosal Immune Responses May Contribute to
  Protection Observed in HIV-1 Exposed-Uninfected
• A practical method of immunization
• tools and methods designed to make access to
  vaccines both simpler and safer (e.g. fewer
  doses, needle-free) are needed (Source WHO
  Department of Vaccines and Biologicals)

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Adjuvants for Mucosally-Administered HIV-1
Vaccines

• Adjuvants are required to augment immune
  responses induced after mucosal immunization with
  peptide/protein immunogens
• Safe adjuvants are needed
• Cholera toxin used as an experimental mucosal
  adjuvant for many years but it has too many
  adverse effects
• Immunogenic, induction of anaphylactic reactions,
  Bells Palsy after nasal immunization with LT in
  humans

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Recombinant Cytokines As Adjuvants for
Nasally-Administered HIV Vaccines
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Peptide IM RC-529 GM-CSF
Peptide IN IL-1/GM-CSF
Peptide IN mCT
Serum IgG
Vaccine 22 (2004) 37743788
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Nasal Immunization of Cynomolgus Macaques with
HIV-1 Peptide and IL-1 GM-CSF

• IL-1 GM-CSF exhibits adjuvant activity by the
  nasal route in cynomolgus macaques.
• No systemic adverse effects (Weight loss, Fever)
• No induction of mucosal anti-HIV IgA
• There is extreme variation in the
  antigen-specific serum IgG titer by animals
  within the same group.
• Nasal immunization is not as effective as
  parenteral immunization in macaques.

Vaccine 22 (2004) 37743788
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Prime-Boost Immunization For Optimal Mucosal
Immunity in Females and Males
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Reproductive Tract HIV-1-Specific IFN-g SFC
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The optimal immunization regimen for females may
not be the same as the optimal immunization
regimen for males.
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Future Studies

• Utilize appropriate animal models to develop
  mucosal immunization strategies that will be
  effective in humans

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Future Studies

• Develop small molecule adjuvants for mucosal
  vaccines
• Effective, non-immunogenic, economical
• Develop dry powder mucosal vaccine formulations
• Longer shelf life, no cold chain
• Bioadhesive to increase immunogenicity

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ACKNOWLEDGMENTS
Tom Tlusty Neil Sparks Cathy Doil Will
Gwinn Shila Nordone James Peacock Greg
Sempowski Barton Haynes