Vaccines that target the production of Abs to gp41 or the MPER

Target region (reference)ImmunogenEpitope supported by membraneAnimalImmunization scheduleaELISA antigenbAb titerc50% Nt titerStrain(s) tested,d assay method
gp41 (134)gp41 fused to C terminus of p15E from PERV and expressed on VSVYesNew Zealand White rabbits2 × 106 PFU VSV recombinant viruses (1st) and boost with purified protein emulsified in incomplete Freund's adjuvant at 3-wk intervals (2nd, 3rd, and 4th); injection route and dose were not specifiedgp41-MPER655-682 expressed on the surface of cellsTiter not tested; presence of Abs shown in Western blot by binding of antisera to cell lysate and using flow cytometryOnly 1/20 dilution testedHXB2 and JRFL, by single-cycle HIV infectivity assay
gp41 (258)DNA vaccine comprising gp41 fused to the C terminus of influenza virus HAYesBALB/c miceMice were immunized with fusion protein alone or displayed on proteoliposomes; 100 μg DNA i.m. 3 times at 4-wk intervalsgp41 fused to N terminus of the SV5 HN proteinMedium40% neutralization at a 1/40 dilution of pooled seraSF162, by single-cycle HIV infectivity assay
MPER and CHR (124)Trimeric gp41 C-terminal domain in proteoliposome or without liposomeYesBALB/c miceTwo i.p. immunizations at a 3-wk interval; dose was not specifiedC terminus of gp41C terminus of gp41 in proteoliposome, medium; C terminus of gp41 without proteoliposome; lowNot NtRF, by syncytium inhibition
MPER (143)MPER649-684 fused to cholera toxin B subunit (MPER/CTB)NoBALB/c micePrime with 42 μg i.n. 5 times every wk and then 2 more either i.p. or i.n. with cholera toxin at wk 10 and 18 or prime with 3.5 μg i.p. adsorped to alum weekly 4 times, followed by i.p. or i.n. administration at wk 10 and 18Synthetic MPER649-684Medium-highNot testedNA
MPER (115)Three gp41-based prefusion constructs expressed on VLPs or on Sf9 insect cells; gp41 fused to C1 and C5 regions of gp120 with other gp120 segments replaced by the SH3 domain of CD2BP1, a 24-aa sequence linking gp120 to gp41 NHR, CHR, MPER, and the TM domain (C1); gp41 NHR, CHR, the MPER, and the TM (C2); trimeric BAFF fused to CHR, MPER, and TM (C3)YesOutbred guinea pigsAll groups received 3 immunizations at 2-wk intervals of 5 × 106 cells i.d. with or without E. coli LT or 2 or 10 μg i.d. or i.m. with or without LT (VLPs)VLPs, soluble C1 that does not contain the MPER and TM, and synthetic peptides bearing the MPER sequence from HIV MN and ADATiters to VLP were high; titers to fusion protein were low to medium; binding to MPER peptide was so low that titers were not measurableNot NtMN, SFI2.LS, ADA, and NL-ADArs, by single-cycle HIV infectivity assay
MPER (122)DNA prime followed by recombinant protein boost with MPER or 4E10 epitope expressed in place of gp120 V1/2NoBALB/c mice and New Zealand White rabbits4 i.m. DNA immunizations (40 μg) at wk 0, 3, 6, and 18 and boost two times with 10 μg protein (s.c.) in Ribi adjuvant at wk 28 and 32 or wk 35 and 39 (mice); prime-boost with 4 i.m. DNA doses (0.5, 1, or 2 mg) at wk 0, 4, 8, and 12 and 3 s.c. protein boosts (50 μg) with Ribi adjuvant plus cell wall skeleton were given at wk 20, 25, and 30 (rabbits); for protein, 5 (100 μg) s.c. immunizations administered at wk 0, 5, 10, 20, and 30 (rabbit)WT JR-FL gp120 and a panel of peptides bearing overlapping sequences from V3 and MPERHigh titers to WT JRFL gp120; no detectable Abs to MPER peptides producedMice, 10-40; rabbits, 10-800JR-FL and SF162 (mice) and JRFL, SF162, MN, HxB2, ADA, and JR-CSF (rabbits), by single-cycle HIV infectivity assay
  • a Immunization routes are abbreviated as follows: intranasal, i.n.; intraperitoneal, i.p.; subcutaneous, s.c.; intramuscular, i.m.; intradermal, i.d.

  • b Amino acid sequences describe synthetic peptides used to determine Ab titers.

  • c Titers are described as follows: low, <1,000; medium, 1,000 to 15,000; medium-high, 15,000 to 50,000; high, 50,000 to 1,000,000; very high, >1,000,000. The difference between endpoint and midpoint titers was not taken into account.

  • d Strains that were neutralized are in boldface type. NA, not applicable.