Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 02 2020
20 02 2020
Historique:
received:
20
09
2019
accepted:
10
12
2019
entrez:
22
2
2020
pubmed:
23
2
2020
medline:
13
11
2020
Statut:
epublish
Résumé
The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) - when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) - to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge. Here we report the preclinical development of recombinant tetanus toxoid heavy chain fragment (rTTHC) linked to FP8 (FP8-rTTHC) as a suitable FP-conjugate vaccine immunogen. We assessed 16 conjugates, made by coupling the 4 most prevalent FP8 sequences with 4 carrier proteins: the aforementioned KLH and rTTHC; the H. influenzae protein D (HiD); and the cross-reactive material from diphtheria toxin (CRM197). While each of the 16 FP8-carrier conjugates could elicit HIV-1-neutralizing responses, rTTHC conjugates induced higher FP-directed responses overall. A Sulfo-SIAB linker yielded superior results over an SM(PEG)2 linker but combinations of carriers, conjugation ratio of peptide to carrier, or choice of adjuvant (Adjuplex or Alum) did not significantly impact elicited FP-directed neutralizing responses in mice. Overall, SIAB-linked FP8-rTTHC appears to be a promising vaccine candidate for advancing to clinical assessment.
Identifiants
pubmed: 32080235
doi: 10.1038/s41598-020-59711-y
pii: 10.1038/s41598-020-59711-y
pmc: PMC7033230
doi:
Substances chimiques
AIDS Vaccines
0
Adjuvants, Immunologic
0
Peptides
0
Recombinant Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3032Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI106878
Pays : United States
Investigateurs
Nadia Amharref
(N)
Christopher Barry
(C)
Boonchai Boonyaratanakornkit
(B)
Elizabeth Carey
(E)
Ria Caringal
(R)
Kevin Carlton
(K)
Naga Chalamalsetty
(N)
Adam Charlton
(A)
Rajoshi Chaudhuri
(R)
Mingzhong Chen
(M)
Peifeng Chen
(P)
Nicole Cibelli
(N)
Jonathan W Cooper
(JW)
Hussain Dahodwala
(H)
Marianna Fleischman
(M)
Julia C Frederick
(JC)
Haley Fuller
(H)
Jason Gall
(J)
Isaac Godfroy
(I)
Deepika Gollapudi
(D)
Daniel Gowetski
(D)
Joe Horwitz
(J)
Althaf Hussain
(A)
Vera Ivleva
(V)
Lisa Kueltzo
(L)
Yile Li
(Y)
Venkata Mangalampalli
(V)
Gabriel Moxey
(G)
Sarah O'Connell
(S)
Aakash Patel
(A)
Erwin Rosales-Zavala
(E)
Elizabeth Scheideman
(E)
Nicole A Schneck
(NA)
Zachary Schneiderman
(Z)
William Shadrick
(W)
Alison Vinitsky
(A)
Xiangchun E Wang
(XE)
Sara Witter
(S)
Yanhong Yang
(Y)
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