• Vaccine Name: V180 - ISCOMATRIX™ adjuvant
• Target Pathogen: Dengue Virus
• Target Disease: Dengue Fever
• Type: investigational recombinant subunit vaccine
• Status: Clinical trial
• Host Species for Licensed Use: None
• Antigen: Truncated dengue envelope proteins (DEN-80E) for all 4 serotypes (Manoff et al., 2019)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A recombinant subunit Dengue Virus vaccine that utilizes 80% of the Envelope protein of all 4 serotypes as the antigen with ISCOMATRIX™ adjuvant (Manoff et al., 2019).

Human Response

• Vaccination Protocol: Among the 98 adults who were randomized into the trial, 57 (58%) were female, 92 (94%) were white, and the mean age was 27 years (range, 18 to 48 years). The gender, race/ethnicity, and age distributions were generally consistent across the treatment groups (data not shown).The first, second, and third injections of trial product were received by 98 (100%), 94 (96%), and 90 (92%) of randomized participants, respectively (Figure 1). Overall, 83 (85%) participants completed the trial. (Manoff et al., 2019)
• Immune Response: Virus Neutralizing Antibody:
  
  Each of the 6 V180 formulations containing ISCOMATRIX™ adjuvant met the pre-specified definition of a positive immune response, with seroconversion rates of ≥85.7% for all 4 dengue serotypes; GMTs ranged from 73 to 1344. Within each V180 dose level, GMTs were slightly higher (within 2-fold) for formulations with 60 ISCO™ units than formulations with 30 ISCO™ units. In contrast, for a given dose level of ISCOMATRIX™ adjuvant, GMTs did not increase with increasing doses of V180 antigen.
  
  All 6 V180 formulations with ISCOMATRIX™ adjuvant had similar profiles: GMTs increased by Month 2 (28 Days Postdose 2), increased further by Month 3 (28 Days Postdose 3), and then declined over time through Month 14 (1 Year Postdose 3), remaining generally above baseline for DENV1, DENV2, and DENV3, and generally returning to baseline for DENV4. During long-term follow-up, GMTs generally remained higher in the 60 ISCO™ unit group than the 30 ISCO™ unit group for the low-dose V180 cohort, but tended to converge in the medium-dose and high-dose V180 cohorts.
  
  Memory B-Cell Responses:
  
  Induction of B-cell memory to each of the four DENV serotypes was observed in peripheral blood mononuclear cells among all participants who received 3 injections of high-dose V180 with ISCOMATRIX™ adjuvant (30 or 60 ISCO™ units) at 28 Days Postdose 3, the mean number of dengue-specific memory B cells in these recipients had increased in frequency by 1 to 2 logs over the pre-vaccination baseline
  
  (Manoff et al., 2019)
• Side Effects: V180 with ISCOMATRIX™ adjuvant was associated with a higher frequency of injection-site AEs (adverse effects) overall, injection-site AEs of erythema or swelling that were ≥5 cm or ≥10 cm, and a higher frequency of injection-site pain/tenderness that participants assessed as severe (defined in the protocol as the inability to do work or usual activities). V180 with ISCOMATRIX™ adjuvant was also associated with higher frequencies of systemic AEs overall, and those assessed by the investigator as related to study product. Fever (temperature ≥38.0°C [100.4°F]) was reported in 5 (9%) ISCOMATRIX™ adjuvant recipients.
  
  (Manoff et al., 2019)