PfSPZ malaria vaccine marks clinical successes
The malaria vaccine candidate PfSPZ (Sanaria) was safe and apparently offered some protection to healthy young African adults in a Phase 1 trial in malaria-endemic Mali. Among the 93 enrolled subjects, 93% in the placebo arm developed the disease in the following transmission season compared to 66% in the vaccine cohort.Citation1
PfSPZ, which consists of live radiation-attenuated Plasmodium falciparum sporozoites, is in several clinical trials testing different dosing regimens including a study recruiting Kenyan infants and children.
In another small trial conducted in Germany, a fully viable non-irradiated variant, PfSPZ-CVac, was safe and protected up to 100% of volunteers concomitantly taking the antimalarial drug chloroquine.Citation2 The best-responding group of 9 subjects, who received three high doses of PfSPZ-CVac, showed no signs of infection in a controlled challenge 10 weeks after the last dose.
“By vaccinating with a live, fully active pathogen, it seems clear that we were able to set of a very strong immune response,” lead author Benjamin Mordmueller of University of Tübingen said. “Additionally, all the data we have so far indicate that what we have here is relatively stable, long-lasting protection.”
- Sissoko MS, Healy SA, Katile A, Omaswa F, Zaidi I, Gabriel EE, Kamate B, Samake Y, Guindo MA, Dolo A, Niangaly A, Niaré K, Zeguime A, Sissoko K, Diallo H, Thera I, Ding K, Fay MP, O'Connell EM, Nutman TB, Wong-Madden S, Murshedkar T, Ruben AJ, Li M, Abebe Y, Manoj A, Gunasekera A, Chakravarty S, Sim BK, Billingsley PF, James ER, Walther M, Richie TL, Hoffman SL, Doumbo O, Duffy PE. Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis 2017; doi: https://doi.org/10.1016/S1473-3099(17)30104-4
- Mordmüller B, Surat G, Lagler H, Chakravarty S, Ishizuka AS, Lalremruata A, Gmeiner M, Campo JJ, Esen M, Ruben AJ, Held J, Calle CL, Mengue JB, Gebru T, Ibáñez J, Sulyok M, James ER, Billingsley PF, Natasha KC, Manoj A, Murshedkar T, Gunasekera A, Eappen AG, Li T, Stafford RE, Li M, Felgner PL, Seder RA, Richie TL, Sim BK, Hoffman SL, Kremsner PG. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature 2017; 542(7642):445-449
Immunotherapy of celiac disease passed a phase 1 trial
A vaccine candidate designed to induce tolerance to gluten was safe and well tolerated in a randomized, placebo-controlled dose-escalating Phase 1b study. The Nexvax2 vaccine (ImmusanT) contains short immunodominant peptides recognized by CD4+ T cells implicated in autoimmune diseases. The trial identified a dose for a planned Phase 2 study, which will investigate the potential to protect against inadvertent exposure to gluten.
There is no treatment for celiac disease—an autoimmune reaction to gluten from wheat, rye and barley—other than dietary restrictions. In the US, the prevalence of celiac disease is around 1%, but ∼80% of cases remain undiagnosed.
This year's influenza vaccine was 48% efficacious according to CDC
The influenza vaccine prevented 48% of medical visits in the US, Centers for Disease Control and Prevention said. In the past decade, the seasonal vaccine's efficacy has fluctuated mostly around 40–50%, with 59% last year and 19% the year before.
Scientists monitor the epidemiology of influenza throughout the year and select strains for vaccine production in the upcoming season. To avoid mismatch, developing a universal influenza vaccine has been a priority for years, although success remains elusive.
Checkpoint inhibition immunotherapy can have lasting effects after discontinuation
Some patients with advanced kidney cancer continued to benefit from immunotherapy even after they had stopped immunotherapy due to adverse events. Of the 19 patients included in a recent study, who had been treated with PD-1 or PD-L1 inhibitors, 8 had durable responses for at least 6 months after they had received the last dose. Prospective studies are planned to validate these results.
MERS vaccine successful in an early trial
The MERS vaccine candidate GLS-5300 (Inovio) was safe and immunogenic in a Phase 1 clinical trial. Significant antigen-specific cytotoxic T-lymphocytes were detected in 92% of 62 healthy volunteers who had been given three doses of the vaccine. All subjects but one developed cell or antibody response.
The DNA vaccine GLS-5300 is the only MERS vaccine candidate in clinical trials. There is no approved treatment for the disease that claimed 700 lives since its emergence in 2012.
DNA vaccine against Zika induces immunity in volunteers
Three doses of the Zika vaccine GLS-5700 (Inovio) elicited virus-specific antibodies in all 39 evaluated healthy volunteers enrolled in a Phase 1 trial. Antibodies were detected in 82% and 40% of subjects after two and one doses, respectively.
The trial builds on successful preclinical studies in which GLS-5700 protected 100% of tested animals against Zika. It is the first time induction of immune responses following immunization has been reported.
Nivolumab approved for bladder cancer
The US Food and Drug Administration (FDA) has approved the PD-1 inhibitor nivolumab (Opdivo, BMS) for the treatment of locally advanced or metastatic urothelial carcinoma that progressed after chemotherapy. Continued approval depends on future confirmatory clinical trials.
The decision is based on results from the CheckMate-275 study, in which one in five patients responded to nivolumab with the median duration of response of 10 months.
FDA lifts clinical hold on a brain cancer vaccine trial
A Phase 3 trial of DCVax personalized glioblastoma immunotherapy (Northwest Biotherapeutics) can continue 18 months after the FDA had suspended enrollment of new patients. While the recruitment of subjects reached only ∼95% of the target number, investigators will be able to proceed to evaluating of the trial within a few months.
DCVax consists of dendritic cells that are exposed to the resected cancerous tissue. The technology is tested in clinical trials with various solid tumors.
Novel vaccine against mosquito saliva aims to protect against a variety of infections
The vaccine AGS-v against four proteins from mosquito salivary glands is being tested in a double-blind placebo-controlled Phase 1 trial. 60 healthy volunteers aged 18–50 will receive two doses of AGS-v with or without adjuvant or placebo, and they will be subjected to uninfected Aedes aegypti bite challenge three weeks later.
The National Institute of Allergy and Infectious Diseases (NIAID) researchers hope that their vaccine will protect against a host of mosquito-borne diseases, such as Zika, malaria, West Nile fever and dengue fever. “Mosquitoes cause more human disease and death than any other animal,” NIAID director Anthony S. Fauci said in a statement. “A single vaccine capable of protecting against the scourge of mosquito-borne diseases is a novel concept that, if proven successful, would be a monumental public health advance.”
Nelipepimut-S immunotherapy can continue clinical trials after prior hold
The breast cancer vaccine nelipepimut-S (NeuVax, Galena) can proceed with Phase 2 trials that were suspended after a Phase 3 study was terminated for futility. The data safety monitoring board has concluded that the current trials, which test the combination of nelipepimut-S and the anti-HER2 receptor antibody trastuzumab, show safety.
Nelipepimut-S vaccine contains a peptide derived from the transmembrane protein HER2, a marker of aggressive forms of breast cancer. It is designed to stimulate CD8+ T-cell response. Nelipepimut-S is administered with the recombinant granulocyte macrophage-colony stimulating factor as adjuvant.
Single low dose of a new Zika vaccine candidate protected mice and monkeys from infection
A lipid nanoparticle-encapsulated RNA vaccine encoding pre-membrane and envelope Zika glycoproteins was successful in a preclinical setting. A single dose induced strong antibody responses and protected from Zika infection in a challenge 5 weeks post-vaccination in both mice and non-human primates.Citation1
“We observed rapid and durable protective immunity without adverse events, and so we think this candidate vaccine represents a promising strategy for the global fight against Zika virus,” senior author Drew Weissman of University of Pennsylvania said. “If a vaccine is effective after just a single immunization, the infrastructure needed for its administration can be much simpler. Production of an mRNA-based vaccine is also likely to be easier and less expensive compared to traditional virus- or viral protein-based vaccines.”
- Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, Dowd KA, Sutherland LL, Scearce RM, Parks R, Wagner W, Granados A, Greenhouse J, Walker M, Willis E, Yu JS, McGee CE, Sempowski GD, Mui BL, Tam YK, Huang YJ, Vanlandingham D, Holmes VM, Balachandran H, Sahu S, Lifton M, Higgs S, Hensley SE, Madden TD, Hope MJ, Karikó K, Santra S, Graham BS, Lewis MG, Pierson TC, Haynes BF, Weissman D. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 2017; doi: https://doi.org/10.1038/nature21428
HIV vaccine might clear the virus reservoir to improve patient's condition
The therapeutic HIV vaccine MVA.HIVconsv was efficacious enough to allow a group of patients stop antiretroviral therapy. Of 11 HIV-positive subjects tested in a small trial, four (36%) continued to remain off antiretroviral drugs (7–22 weeks). Seven had to resume therapy within 4 weeks.
The vaccine, which targets a highly conserved region in HIV-1, was administered in two prime-boost doses three weeks apart. In addition, patients were given romidepsin to reactivate the reservoir of latent viruses (the so-called kick-and-kill strategy).