A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals

  1. Nathan B. Erdmann
  2. Wilton B. Williams
  3. Stephen R. Walsh
  4. Nicole Grunenberg
  5. Paul T. Edlefsen
  6. Paul A. Goepfert
  7. Derek W. Cain
  8. Kristen W. Cohen
  9. Janine Maenza
  10. Kenneth H. Mayer
  11. Hong Van Tieu
  12. Magdalena E. Sobieszczyk
  13. Edith Swann
  14. Huiyin Lu
  15. Stephen C. De Rosa
  16. Zachary Sagawa
  17. M. Anthony Moody
  18. Christopher B. Fox
  19. Guido Ferrari
  20. R.J. Edwards
  21. Priyamvada Acharya
  22. S. Munir Alam
  23. Robert Parks
  24. Margaret Barr
  25. Georgia D. Tomaras
  26. David C. Montefiori
  27. Peter B. Gilbert
  28. M. Juliana McElrath
  29. Lawrence Corey
  30. Barton F. Haynes
  31. Lindsey R. Baden
  32. NIAID HVTN 133 Study Group
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Abstract

Background

HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys.

Methods

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 recruited between 15 July 2019 and 18 October 2019 and 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.

Results

The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations.

Conclusions

MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for 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>

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