Title: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

Journal Article · · npj Vaccines
ORCiD logo [1];  [2];  [3];  [3]; ORCiD logo [4];  [3];  [3];  [3]; ORCiD logo [3];  [1];  [1];  [1]; ORCiD logo [5];  [1];  [1];  [6];  [1]; ORCiD logo [3];  [3]; ORCiD logo [4] more »; ORCiD logo [3]; ORCiD logo [3]; ORCiD logo [3]; ORCiD logo [7]; ORCiD logo [1]; ORCiD logo [8] « less
  1. Univ. of Amsterdam (Netherlands); Amsterdam Institute for Infection and Immunity (Netherlands)
  2. Univ. of Oxford (United Kingdom)
  3. The Scripps Research Inst., La Jolla, CA (United States)
  4. University of Southampton (United Kingdom)
  5. Univ. of Amsterdam (Netherlands); Amsterdam Institute for Infection and Immunity (Netherlands); All India Institute of Medical Sciences, New Delhi (India)
  6. Univ. of Amsterdam (Netherlands); Biomedical Primate Research Centre, Rijswijk (Netherlands)
  7. Univ. of Oxford (United Kingdom); Kumamoto University (Japan)
  8. Univ. of Amsterdam (Netherlands); Amsterdam Institute for Infection and Immunity (Netherlands); Cornell Univ., Ithaca, NY (United States). Weill Medical College

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
Aids Fonds Netherlands; Bill and Melinda Gates Foundation; National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
2471725
Journal Information:
npj Vaccines, Journal Name: npj Vaccines Journal Issue: 1 Vol. 9; ISSN 2059-0105
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

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