An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals

  1. Nathaniel Erdmann
  2. Wilton B. Williams
  3. Stephen R. Walsh
  4. Derek W. Cain
  5. Matthew Clark
  6. Ryan Tuck
  7. Sommer Holmes
  8. Benae Clardy
  9. Andrew Foulger
  10. Robert Parks
  11. Margaret Barr
  12. Amanda Eaton
  13. Kevin O. Saunders
  14. Nicole Grunenberg
  15. Paul Edlefsen
  16. Paul A. Goepfert
  17. Kristen W. Cohen
  18. Janine Maenza
  19. Kenneth Mayer
  20. Hong Van Tieu
  21. Magdalena E. Sobieszczyk
  22. Edith Swann
  23. Huiyin Lu
  24. Stephen C. De Rosa
  25. Zachary K. Sagawa
  26. Bob C. Lin
  27. Robin E. Carrol
  28. Krisha McKee
  29. Nicole A. Doria-Rose
  30. Mark K. Louder
  31. M. Anthony Moody
  32. Christopher B. Fox
  33. Guido Ferrari
  34. Robert J. Edwards
  35. Priyamvada Acharya
  36. S. Munir Alam
  37. Georgia D. Tomaras
  38. David C. Montefiori
  39. Peter B. Gilbert
  40. M. Juliana McElrath
  41. Lawrence Corey
  42. Barton F. Haynes
  43. Lindsey R. Baden
  44. the NIAID HVTN 133 Study Group
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Abstract

Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in monkeys. The HVTN133 phase 1 clinical trial (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03934541">NCT03934541</ext-link>) studied the MPER peptide-liposome immunogen in 24 HIV-1 seronegative individuals. Participants were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. The trial was stopped prematurely due to an anaphylaxis reaction in one participant attributed to vaccine-associated polyethylene glycol. The immunogen induced MPER-specific serum antibodies and CD4+ T-cell responses in 95% and 85% of vaccinees, respectively, and 35% of vaccine recipients had circulating IgG+ memory B cells with an MPER-bnAb binding phenotype. Affinity purification of plasma MPER-specific IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations and tier 2 HIV-1 neutralizing B cell clonal lineages were isolated from MPER-reactive B cells. These results demonstrate that the HIV gp41 MPER region is a promising target for induction of heterologous neutralizing antibodies by a candidate HIV vaccine.

Trial Registration

<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov/">http://www.clinicaltrials.gov/</ext-link> Identifier: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03934541">NCT03934541</ext-link>

Funding

National Institutes of Health, Bill and Melinda Gates Foundation

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