DC vaccine shows promise in late-stage ovarian cancer
A personalized dendritic cell (DC) vaccine improved two-year survival in patients with ovarian cancer that recurred after previous platinum chemotherapy.Citation1 The vaccine, which consists of autologous DCs primed in vitro with the patient's tumor lysate, was well tolerated and induced T-cell responses against tumor neoantigens. The clinical trial enrolled 25 patients. The vaccine was most effective when combined with the anti-VEGF MAb bevacizumab and chemotherapeutic cyclophosphamide. Ovarian cancer remains undiagnosed until it reaches late stage in the majority of cases. The 5-year survival is <20% for stage 4.
- Tanyi JL, Bobisse S, Ophir E, Tuyaerts S, Roberti A, Genolet R, Baumgartner P, Stevenson BJ, Iseli C, Dangaj D, Czerniecki B, Semilietof A, Racle J, Michel A, Xenarios I, Chiang C, Monos DS, Torigian DA, Nisenbaum HL, Michielin O, June CH, Levine BL, Powell DJ Jr., Gfeller D, Mick R, Dafni U, Zoete V, Harari A, Coukos G, Kandalaft LE. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci Transl Med 2018;10(436). doi:10.1126/scitranslmed.aao5931. PMID:29643231.
An investigational 15-valent pneumococcal vaccine is tested in Phase 3 trials
Safety and immunogenicity will be investigated in two Phase 3 studies of the 15-valent pneumococcal conjugate vaccine V114 (Merck). The trials will compare V114 to the widely used Prevnar 13 (Pfizer); both vaccines will be administered with Pneumovax 23 (Merck) as a booster.
The first part enrolls 600 healthy adults aged ≥50 years, who will receive the booster vaccine after one year. In the second part, Pneumovax 23 will be administered 8 weeks after the first immunization in the sample of 300 HIV-infected adults.
Pembrolizumab improves survival in non-squamous NSCLC
The anti-PD-1 MAb pembrolizumab (Keytruda, Merck) in combination with chemotherapy almost doubled progression-free survival in the randomized, placebo-controlled Phase 3 KEYNOTE-189 trial.Citation1 One-year survival was 70% in the experimental group compared to 50% in the placebo plus chemotherapy cohort. The study enrolled >600 patients with metastatic non-squamous non-small cell lung cancer (NSCLC).
Based on these results, the US Food and Drug Administration (FDA) has granted the combination treatment a priority review. If approved, metastatic NSCLC would become the third indication for which pembrolizumab is approved.
- Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC, KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. N Engl J Med 2018; doi:10.1056/NEJMoa1801005.
Ebola vaccine is immunogenic for at least two years
A single administration of the Ebola vaccine rVSV-ZEBOV (Merck) elicited viral glycoprotein-specific antibodies that persisted for at least two years in a Phase 1 trial in Europe.Citation1 Of 44 participants who received a high dose and 37 who received a lower dose, 100% and 90%, respectively, remained seropositive after two years. However, the neutralizing antibody levels decreased to less than one-third peak levels within 6 months from vaccination. Previously, rVSV-ZEBOV showed 100% efficacy in a ring vaccination study in endemic Guinea.
- Huttner A, Agnandji ST, Combescure C, Fernandes JF, Bache EB, Kabwende L, Ndungu FM, Brosnahan J, Monath TP, Lemaître B, Grillet S, Botto M, Engler O, Portmann J, Siegrist D, Bejon P, Silvera P, Kremsner P, Siegrist CA, VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis 2018; doi:10.1016/S1473-3099(18)30165-8. PMID:29627147.
Next season's influenza vaccine might be only 20% effective, study suggests
The efficacy of the next seasonal influenza vaccine might again be as low as 20%, according to a modeling study, which utilized the pEpitope method of prediction.Citation1 Interim analysis by the US Centers for Disease Control and Prevention estimated the efficacy of the last year's vaccine against the severe H3N2 strain at 25%.Citation2 The World Health Organization (WHO) has recommended a different strain of H3N2 for the production of the next vaccine.
“The vaccine has been changed for 2018–19, but unfortunately it still contains two critical mutations that arise from the egg-based vaccine production process,” senior author Michael Deem of Rice University said. “Our study found that these same mutations halved the efficacy of flu vaccines in the past two seasons, and we expect they will lower the efficacy of the next vaccine in a similar manner.”
- Bonomo ME, Deem MW. Predicting influenza H3N2 vaccine efficacy from evolution of the Dominant Epitope. Clin Infect Dis 2018; doi:10.1093/cid/ciy323.
- Flannery B, Chung JR, Belongia EA, McLean HQ, Gaglani M, Murthy K, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Foust A, Sessions W, Berman L, Barnes JR, Spencer S, Fry AM. Interim estimates of 2017–18 seasonal influenza vaccine effectiveness — United States, February 2018. MMWR Morb Mortal Wkly Rep 2018;67(6):180–5. doi:10.15585/mmwr.mm6706a2. PMID:29447141.
A new peanut allergy immunotherapy effective in a preclinical study
A nanoemulsion-adjuvanted intranasal peanut vaccine suppressed allergic reactions in mice and protected them from anaphylaxis.Citation1 The vaccine is designed to elicit TH1 and TH17 immune responses and to suppress the TH2 profile typical for allergic reactions.
“We're changing the way the immune cells respond upon exposure to allergens,” lead author Jessica O'Konek of University of Michigan said. “By redirecting the immune responses, our vaccine not only suppresses the response but prevents the activation of cells that would initiate allergic reactions.”
The immune responses were assessed after 3 monthly doses. Potential long-term effects are being investigated.
- O'Konek JJ, Landers JJ, Janczak KW, Goel RR, Mondrusov AM, Wong PT, Baker JR Jr. Nanoemulsion adjuvant–driven redirection of TH2 immunity inhibits allergic reactions in murine models of peanut allergy. J Allergy Clin Immunol 2018; doi:10.1016/j.jaci.2018.01.042. PMID:29655584.
Universal influenza vaccine candidate is tested in a Phase 2 trial
120 adults 18–49 years of age are being recruited for a placebo-controlled study of the universal influenza vaccine M-001 (BiondVax) in the US. Two injections of the vaccine will be followed by the administration of an unadjuvanted quadrivalent vaccine several weeks later.
M-001, which contains nine epitopes shared by various strains of both influenza A and B, will also be tested in a Phase 3 trial in Eastern Europe, which will enroll almost 10,000 participants aged ≥50 years.
Combination immunotherapy improved survival in a preclinical mesothelioma model
The investigational mesothelin-specific fusion protein VIC-008 together with the immunostimulant AMD3100 (plerixafor) more than doubled survival of mice with malignant mesothelioma.Citation1
“Mesothelioma, a tumor that is caused by asbestos exposure, has been extremely hard to treat; and patients usually survive only 12 to 18 months after diagnosis,” senior author Mark Poznansky of Harvard Medical School said.
VIC-008 is a fusion of single-chain mesothelin-specific antibody fragment and the immunostimulating Hsp70 protein from Mycobacterium tuberculosis. AMD3100, a CXCR4 antagonist, was previously approved for stimulation of stem cell production prior to bone marrow transplantation. The combination changed immunosuppressive Tregs within the mesothelioma tumor into helper-like cells that inhibited tumor growth.
- Li B, Zeng Y, Reeves PM, Ran C, Liu Q, Qu X, Liang Y, Liu Z, Yuan J, Leblanc PR, Ye Z, Sluder AE, Gelfand JA, Brauns TA, Chen H, Poznansky MC. AMD3100 Augments the efficacy of mesothelin-targeted, immune-activating VIC-008 in mesothelioma by modulating intratumoral immunosuppression. Cancer Immunol Res 2018;6(5):539–51. doi:10.1158/2326-6066.CIR-17-0530. PMID:29511032.
Vaccination with Dengvaxia should be preceded by a diagnostic test, according to WHO
WHO has changed its recommendation for the dengue vaccine Dengvaxia (Sanofi) to include a test of prior dengue infection. If the subject has not been exposed to the virus, the vaccine should not be administered. No such diagnostic test yet exists.
The measure follows the finding that immunization with Dengvaxia can exacerbate symptoms of subsequent infections in dengue-naïve individuals. A nationwide vaccination program in the endemic Philippines has been suspended in response, and local officials claim three deaths have been reported due to vaccination.
Meningococcal vaccine Trumenba received a breakthrough designation for young children
The FDA has granted breakthrough designation to the meningococcal B vaccine Trumenba (Pfizer) for use in children aged 1–9 years. The vaccine is approved for young people 10–25 years of age, for whom the burden of MenB is highest. The FDA decision was supported by Phase 2 trial data.
Trumenba is a recombinant vaccine composed of two variants of lipidated factor H binding protein from Neisseria meningitidis serogroup B.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.