Therapeutic herpes vaccine GEN-003 benefits patients in a Phase 2 trial
The genital herpes vaccine GEN-003 (Genocea) reduced the rate of lesions by 40% in a small-scale, placebo-controlled Phase 2b study. 131 patients received a low dose of GEN-003 and were monitored daily. 6 months after treatment, the experimental group showed a 4.5% rate of genital lesions compared to 7.9% in the placebo cohort.
The vaccine targets an antigen from the herpes simplex virus type-2, which is responsible for the majority of disease affecting around 4.5 million people in the U.S. The disease is treated by oral antivirals, which deal with the symptoms but–unlike GEN-003–do not prevent transmission.
Malaria vaccine candidate successful in early trial
The malaria vaccine PfSPZ (Sanaria) protected 90% of 28 adult volunteers in a controlled challenge with the Plasmodium falciparum parasite. The rate of protection was 57% after 24 weeks, and all subjects who received placebo developed the disease.1
The vaccine, which contains live attenuated P. falciparum sporozoites, is injected into the blood in three or five doses. It is moving into larger trials in Kenya and Equatorial Guinea.
1.Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, Chakravarty S, Stafford A, Ruck RC, Eappen AG, Li T, Billingsley PF, Manoj A, Silva JC, Moser K, Nielsen R, Tosh D, Cicatelli S, Ganeshan H, Case J, Padilla D, Davidson S, Garver L, Saverino E, Murshedkar T, Gunasekera A, Twomey PS, Reyes S, Moon JE, James ER, Kc N, Li M, Abot E, Belmonte A, Hauns K, Belmonte M, Huang J, Vasquez C, Remich S, Carrington M, Abebe Y, Tillman A, Hickey B, Regules J, Villasante E, Sim BK, Hoffman SL. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insights 2017; 2(1):e89154
RAS vaccine may have increased survival in early trial with pancreatic cancer patients
63% of 19 patients with resected pancreatic cancer were alive two years after immunization with RAS peptide vaccine TG01 (Targovax) and GM-CSF adjuvant. Similar studies with the standard-of-care chemotherapy showed two-year survival of 30–50%. The open-label Phase 1/2 study took place in UK and Norway. Subjects were administered 36 injections of the vaccine and continued to receive chemotherapy treatment.
The mutated RAS protein used in the vaccine is present in many cancers and is associated with poor prognosis.
A Clostridium difficile vaccine candidate passed Phase 2 test
The C. difficile vaccine PF-06425090 (Pfizer) was safe and immunogenic in healthy adults 65–85 years of age. The vaccine is designed to elicit antibody responses to the two major toxins produced by the bacterium.
C. difficile is a leading cause of nosocomial infections and is a growing concern due to antibiotic resistance. It causes life-threatening diarrhea and colitis. There are almost half a million cases in the U.S. alone, 20% of which recur after treatment.
Pembrolizumab might help patients with mucosal melanoma and bladder cancer
The PD-1 inhibitor pembrolizumab (Keytruda, Merck) showed promise in two Phase 3 clinical trials.
The KEYNOTE trial recruited, among others, 84 patients with advanced mucosal melanoma. 16 of them responded to the treatment with some having no signs of disease progression after 27 months. Mucosal melanoma has a poor prognosis and no known cause. “The data presented here are important because they prove that patients with mucosal melanoma can benefit from anti-PD-1 therapy and should not be excluded from this treatment,” Marcus Butler of Princess Margaret Cancer Centre in Toronto said.
In another KEYNOTE trial, pembrolizumab also extended overall survival with fewer side effects in subjects with previously treated advanced urothelial cancer compared to chemotherapy (10.3 vs. 7.4 months). The objective response rates were 21% and 11%, respectively.
Pembrolizumab also is being tested in combination with the Prophage vaccine (Agenus) in 45 patients with newly diagnosed glioblastoma. Prophage is an individualized heat shock protein-based vaccine prepared from the patients' tumors. This double-blind randomized Phase 2 trial will evaluate efficacy of the combination relative to pembrolizumab monotherapy.
RSV vaccine re-enters Phase 2 trial after previous failure
A respiratory syncytial virus (RSV) vaccine candidate (Novavax) is being tested in a placebo-controlled Phase 2 study with 300 adults 60 years of age and older. The trial, which takes place in the southern hemisphere outside of RSV season, tests the F-protein recombinant nanoparticle vaccine with or without Matrix-M adjuvant.
This candidate failed to meet primary and secondary endpoints of a Phase 3 trial in fall 2016. It is also being tested in children and pregnant mothers.
Combination of checkpoint inhibitors is tested in rare tumors
A clinical trial testing combination immunotherapy has started in a variety of rare cancers. The DART study will administer the anti-PD-1 and anti-CTLA-4 MAbs nivolumab and ipilimumab (both BMS) to 300 patients in the US. Scientists will monitor survival, tumor shrinkage and immunogenicity, along with the genome signatures of the various rare tumors, which account for 20% of all cancers worldwide.
International coalition for prevention of future epidemics has been launched
Coalition for Epidemic Preparedness Innovations (CEPI) was announced at the World Economic Forum. The aim of this global partnership is to develop vaccines against infectious diseases that might cause future epidemics. It comes as a response to the very rapid spread of the recent Ebola and Zika outbreaks at a time when no vaccines were available in the field.
With initial funding from the Bill and Melinda Gates Foundation, Britain's Wellcome Trust and the governments of Japan, Norway and Germany, CEPI's first priority is to develop vaccines against MERS, Lassa fever and Nipah.
Chimeric broadly neutralizing antibodies hold promise for treating HIV infection
99% of tested HIV-1 strains were neutralized by a chimeric broadly neutralizing antibody (bnAb) constructed from memory B cells and blood plasma isolated from an HIV patient.1 Researchers used mass spectrometry and sequencing to determine plasma and B-cell antibodies, respectively. They focused on bnAbs that target the membrane-proximal external region of an HIV-1 envelope glycoprotein, which are not readily made by infected subjects. The team is now trying to develop a vaccine that would elicit similar bnAbs in mice.
1.Williams LD, Ofek G, Schätzle S, McDaniel JR, Lu X, Nicely NI, Wu L, Lougheed CS, Bradley T, Louder MK, McKee K, Bailer RT, O'Dell S, Georgiev IS, Seaman MS, Parks RJ, Marshall DJ, Anasti K, Yang G, Nie X, Tumba NL, Wiehe K, Wagh K, Korber B, Kepler TB, Alam SM, Morris L, Kamanga G, Cohen MS, Bonsignori M, Xia SM, Montefiori DC, Kelsoe G, Gao F, Mascola JR, Moody MA, Saunders KO, Liao HX, Tomaras GD, Georgiou G, Haynes BF. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Sci Immunol 2017; doi: 10.1126/sciimmunol.aal2200
Prostate cancer vaccine failed clinical trial
The prostate cancer vaccine CV9104 (CureVac) failed to meet the primary endpoint in a Phase 2b trial with patients suffering from asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The vaccine did not improve overall survival or progression-free survival in comparison to placebo.
CV9104 is an mRNA vaccine encoding antigens overexpressed in prostate tumors. It had a good safety profile in earlier trials, and the company plans to test the vaccine in combination with other immunotherapy approaches.
Vaccinating healthcare workers might do little to prevent influenza in patients
Data on influenza vaccination of healthcare workers do not unequivocally show protection of patients, according to a study which reviewed four randomized controlled trials in long-term medical facilities.1 While the original studies are often taken as an argument for mandating vaccination in healthcare workers, their results are exaggerated and implausible, according to lead author Gaston De Serres of Laval University.
“If you are making something like flu vaccination mandatory, and enforcing it for healthcare workers, you need to demonstrate that the intervention is effective. But we do not know what percentage of influenza cases can be reduced by vaccinating healthcare workers.”
1.De Serres G, Skowronski DM, Ward BJ, Gardam M, Lemieux C, Yassi A, Patrick DM, Krajden M, Loeb M, Collignon P, Carrat F. Influenza Vaccination of Healthcare Workers: Critical Analysis of the Evidence for Patient Benefit Underpinning Policies of Enforcement. PLOS One 2017; 12(1):e0163586