Immunotherapy of brain cancer shows promise in a Phase 2 trial
The cancer vaccine candidate SurVaxM (MimiVax) was well tolerated and stopped disease progression in 97% of patients with newly diagnosed glioblastoma. In a Phase 2 trial, which enrolled 63 subjects, the one-year survival rate was 94% compared with 65% as typical for this type of cancer.
SurVaxM, which received the orphan drug designation by the US Food and Drug Administration in 2017, is a vaccine targeting survivin, an apoptosis inhibitor highly expressed in glioblastoma cells. It was administered together with standard-of-care chemotherapy and radiation therapy.
The benefit of this combination treatment was seen irrespective of the methylation status of the MGMT gene, which is a marker for prognosis and response to chemotherapy in glioblastoma patients.
Chikungunya vaccine candidate is immunogenic in a mid-stage trial
The Chikungunya vaccine candidate MV-CHIK (Themis) induced neutralizing antibodies in up to 100% of healthy subjects enrolled in a dose-escalating, randomized, double-blind, placebo-controlled Phase 2 study. The vaccine utilizes a measles virus vector, and the study showed that prior vaccination with an MMR vaccine (Priorix, GSK) did not affect immunogenicity.
There is no vaccine or treatment of the mosquito-borne chikungunya infection, which causes joint pains and affects mostly African countries.
Checkpoint inhibition immunotherapy might be more effective in obese patients
Obese subjects with cancer reported better clinical outcomes than non-obese subjects after treatment with PD-1 inhibitors.1 The effect was observed in mice as well as patients with melanoma. Obesity is associated with higher risk of cancer and poorer prospects. One explanation, uncovered in the study, might be that obese individuals produce more PD-1 protein, leading to increased tumor growth prior to treatment and higher efficacy of the antibody in targeting the tumor.
“We are not advocating for obesity as improving prognosis for cancer patients. But obesity appears to induce immune suppression and accelerated tumor growth through mechanisms that can be successfully reversed by checkpoint inhibitor immunotherapy,” co-senior author Arta Monjazeb of University of California Davis said.
1. Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, Mirsoian A, Minnar CM, Stoffel KM, Sturgill IR, Grossenbacher SK, Withers SS, Rebhun RB, Hartigan-O’Connor DJ, Méndez-Lagares G, Tarantal AF, Isseroff RR, Griffith TS, Schalper KA, Merleev A, Saha A, Maverakis E, Kelly K, Aljumaily R, Ibrahimi S, Mukherjee S, Machiorlatti M, Vesely SK, Longo DL, Blazar BR, Canter RJ, Murphy WJ, Monjazeb AM. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med 2018; doi: 10.1038/s41591-018-0221-5
Chickenpox outbreak in a US school with high exemption rate
36 children have contracted chickenpox in a Waldorf school in North Carolina. It is the largest outbreak in the state since the chickenpox vaccine was introduced in 1995. The school has one of the largest vaccine exemption rates, with 110 of 150 children not having been vaccinated against the disease.
Although North Carolina requires pediatric vaccinations for admission to kindergartens, it does allow exemptions for medical or religious reasons. The chickenpox vaccine is almost 100% effective with an excellent safety record, according to the US Centers for Disease Control and Prevention.
Phase 2 trial started for a celiac disease vaccine
The celiac disease vaccine candidate Nexvax2 (ImmusanT) will be tested for safety and efficacy in a randomized, double-blind, placebo-controlled Phase 2 study, which enrolls 150 patients with the immune recognition allele HLA-DQ2.5 who have followed gluten-free diet for at least one year.
The subcutaneous peptide vaccine is designed to reprogram proinflammatory T cells, thereby protecting from overreaction of the immune system to gluten exposure. It was shown safe and well tolerated in a Phase 1 study.
A fractional dose of yellow fever vaccine is sufficient for protection
10-year protection is conferred by one-fifth the standard dose of the 17D-YFV yellow fever vaccine, with no need for a booster.1 In a long-term study, 39 of 40 participants who received a fractional intradermal dose had neutralizing antibodies after 10 years, compared to 34 of 35 who received standard subcutaneous dose of the vaccine.
The findings suggest that small-dose vaccination might be a good strategy for mass vaccination campaigns, since depleted stock is a frequent obstacle to prevention of outbreaks.
There is no cure to the mosquito-borne yellow fever infection, which leads to acute hemorrhagic disease. A 2015-6 outbreak in sub-Saharan Africa claimed the lives of almost 400 people.
1. Roukens AHE, van Halem K, de Visser AW, Visser LG. Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial. Ann Intern Med 2018; 169(11):761-765
Vaccine against Parkinson’s disease successful in preclinical studies
The vaccine candidate UB-312 (United Neuroscience) selectively targeted, and prevented the accumulation of, the toxic form of α-synuclein in cultured cells and mice. Aggregated α-synuclein protein forms insoluble fibrils in the CNS leading to Parkinson’s disease, the second most common neurodegenerative disease affecting 7 million people around the world.
The synthetic vaccine was designed after studying memory B-cells from elderly subjects who spontaneously developed antibodies against aggregated α-synuclein.
A Zika vaccine candidate has positive Phase 1 results
The Zika vaccine candidate VLA1601 (Valneva & Emergent BioSolutions) was safe and immunogenic in an early study. According to interim results at the 2-month point post-vaccination, the seroconversion rate was up to 85% among 67 healthy adults enrolled for the trial, which tested two dose levels, each administered twice 7 or 28 days apart against a placebo.
The aluminum-adjuvanted VLA1601 is a purified inactivated vaccine against the Zika virus, which is a mosquito-borne flavivirus endemic for tropical areas of the world. The infection is most dangerous when contracted by pregnant women, causing microcephaly in unborn babies.
A shingles vaccine candidate advances to clinical trials
The herpes zoster vaccine candidate CRV-101 (Curevo) started a Phase 1 trial to determine its safety, tolerability and immunogenicity. The study takes place in the US and enrolls healthy adults. Shingles follows the reactivation of the varicella zoster virus, which causes chickenpox in childhood and remains persistent in the body until reactivated, resulting in zoster. The disease leads to painful rash typically in the elderly population.
Passive immunization with llama-derived bnAbs protects mice from influenza
Broadly neutralizing antibodies derived from llamas protected mice from infection by most influenza strains of both A and B type.1 The researchers first immunized llamas with an influenza vaccine and identified in their blood four single-domain antibodies specific for the hemagglutinin stem, which they combined into a multidomain antibody (named MD3606) engineered into an adenovirus vector.
Experimental animals, which were immunized intranasally with MD3606, were protected from lethal infection with H1N1, H3N2, H7N9, and B viruses. Passive immunization with MD3606 was also shown to be superior to existing bnAbs against influenza.
1. Laursen NS, Friesen RHE, Zhu X, Jongeneelen M, Blokland S, Vermond J, van Eijgen A, Tang C, van Diepen H, Obmolova G, van der Neut Kolfschoten M, Zuijdgeest D, Straetemans R, Hoffman RMB, Nieusma T, Pallesen J, Turner HL, Bernard SM, Ward AB, Luo J, Poon LLM, Tretiakova AP, Wilson JM, Limberis MP, Vogels R, Brandenburg B, Kolkman JA, Wilson IA. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. Science 2018; 362(6414):598-602
Dried formulation of polio vaccine is effective in preclinical study
A lyophilized heat-stable Sabin inactivated poliovirus vaccine rehydrated after 4 weeks at ambient temperature induced neutralizing antibodies and full protection in a mouse challenge model.1
Polio, which causes lifelong paralysis, has been almost eradicated worldwide, with only 22 new cases in 2017. An effective vaccine that could be delivered to remote areas without the need of refrigeration might lead to complete elimination of poliovirus infection.
1. Shin WJ, Hara D, Gbormittah F, Chang H, Chang BS, Jung JU. Development of Thermostable Lyophilized Sabin Inactivated Poliovirus Vaccine. MBio 2018; doi: 10.1128/mBio.02287-18