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Exploiting vita-PAMPs in vaccines

J Magarian Blander1, Gaetan Barbet2

  • 1The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA; Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Cornell University, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Current Opinion in Pharmacology
|June 12, 2018
PubMed

Insights

Live vaccines use unique microbial signals called vita-PAMPs to boost immunity. These signals, like cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA), enhance adaptive immune responses for better protection.

Area of Science:

  • Immunology
  • Vaccinology
  • Molecular Biology

Background:

  • Live attenuated vaccines induce superior protective immunity compared to inactivated vaccines.
  • Innate immune cells recognize microbial viability through distinct pathogen-associated molecular patterns (PAMPs) termed vita-PAMPs.
  • Two key vita-PAMPs identified are cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA).

Purpose of the Study:

  • To review the molecular mechanisms underlying the adjuvanticity of vita-PAMPs.
  • To discuss the application of vita-PAMPs in designing more effective vaccines.
  • To highlight how vita-PAMPs leverage innate immune pathways to enhance adaptive immunity.

Main Methods:

  • Review of existing literature on vita-PAMPs and their interaction with innate immune receptors.
  • Analysis of molecular pathways activated by c-di-AMP and bacterial mRNA.
  • Examination of how these pathways influence adaptive immune responses, including T cell and antibody production.

Main Results:

  • c-di-AMP from live Gram-positive bacteria stimulates STING-dependent type-I interferon production.
  • Prokaryotic mRNA from live bacteria is recognized by TLR8, distinguishing live from dead microbes.
  • Bacterial mRNA from live Gram-negative bacteria induces heightened type-I interferon and NLRP3 inflammasome activation.
  • Vita-PAMPs enhance adaptive immunity, promoting follicular T helper cell and antibody responses.

Conclusions:

  • Vita-PAMPs are crucial molecular components that confer enhanced adjuvanticity to live vaccines.
  • Understanding vita-PAMP mechanisms allows for the rational design of next-generation vaccines with improved efficacy.
  • Targeting vita-PAMP-mediated innate immune activation holds significant promise for developing superior vaccine strategies.

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