Human Vaccines & Immunotherapeutics: news

Artificial intelligence predicts responders to cancer immunotherapy

Overall survival and responsiveness to checkpoint inhibition immunotherapy in non-small cell lung cancer were successfully predicted by a computer program trained on a sample of 50 CT scans.¹ The algorithm recognized changes in the texture, volume and shape of the cancerous lesions, not just their size, which is typical for diagnosis by doctors.

Only ~20% of the cancer patients respond to checkpoint inhibition immunotherapy overall, and identifying responders prior to treatment would bring considerable cost savings.

“[Immunotherapy] remains extremely expensive – about $200,000 per patient, per year,” senior author Anant Madabhushi of Case Western Reserve University said, “That’s part of the financial toxicity that comes along with cancer and results in about 42% of all newly diagnosed cancer patients losing their life savings within a year of diagnosis.”

Dengue vaccine candidate was 80% effective in a late-stage trial

The dengue vaccine TAK-003 (Takeda) prevented 80% of the cases and 95% of the hospitalizations in the Phase 3 Tides study.² A total of 20,000 participants aged 4–16 years, enrolled in dengue-endemic countries of Latin America and Asia, received two doses of TAK-003 or placebo in a 2:1 ratio. Vaccine efficacy varied from 70% to 98% depending on serotype.

Notably, the vaccine was 75% efficacious in subjects with no prior dengue exposure. The only marketed vaccine against dengue, Dengvaxia (Sanofi), was shown to exacerbate infection in these people.

Pembrolizumab beneficial in prostate and head-and-neck cancers

Five percent of the men with end-stage prostate cancer reported tumor shrinkage or clearance following treatment with the anti-PD-1 MAb pembrolizumab (Merck) in a Phase 2 trial.³ Notably, half of these patients were alive and tumor-free after 2 years of therapy. Nineteen percent showed some response with decrease in the cancer-associated prostate-specific antigen.

“We don’t see much activity from the immune system in prostate tumors, so many oncologists thought immunotherapy wouldn’t work for this cancer type. But our study shows that a small proportion of men with end-stage cancer do respond,” senior author Johann de Bono of Royal Marsden Hospital said. “We found that men with mutations in DNA repair genes respond especially well to immunotherapy.”

Another Phase 3 study involving almost 900 subjects found pembrolizumab to be superior to chemotherapy in advanced head-and-neck cancer,⁴ upholding recent approval by the European Medicines Agency (EMA) as a first-line treatment. Combination of the immunotherapeutic with chemotherapy extended survival in all patients, while pembrolizumab alone was sufficient in patients with high PD-L1 levels.

Smallpox vaccine proves superior immunogenicity and safety

The smallpox and monkeypox vaccine MVA-BN (Bavarian Nordic) was better tolerated and induced comparable antibody responses as the other licensed vaccine ACAM2000 (Emergent BioSolutions) in a Phase 3 trial.⁵

In the study, which is the last piece of evidence to support the registration already approved by the U.S. Food and Drug Administration (FDA), >400 participants were randomized to receive MVA-BN followed by ACAM2000, or ACAM2000 alone. The combination of vaccines induced almost twofold higher antibody responses and significantly attenuated the major cutaneous reaction indicative of protection from variola infection.

First ebola vaccine approved in Europe

The European Medicines Agency (EMA) has approved the Ebola vaccine rVSV-ZEBOV-GP (Merck). The decision will allow stockpiling and wider distribution of the vaccine, which was shown to be almost 100% effective in an outbreak setting.

The single-dose rVSV-ZEBOV-GP, which targets the Zaire strain of Ebola, has been administered to 250,000 people in the Democratic Republic of the Congo (DRC), where an ongoing outbreak has claimed >11,000 lives.

DRC officials have started the roll-out of a second vaccine, Ad26.ZEBOV/MVA-BN (J&J), which will be administered to 50,000 people in the city of Goma. EMA has received an application for approval of this vaccine, which is administered in two doses 56 days apart and has never been tested in the field.

Tri-specific antibody technology suppressed myeloma in a preclinical trial

Antibodies engineered to recognize three different epitopes stimulated antitumor immune responses in a mouse model of myeloma.⁶ The tri-specific antibody brings into close proximity T cells and tumor cells by targeting the myeloma-associated CD38 epitope, and two T-cell epitopes: the T-cell receptor component CD3 and the co-stimulatory receptor CD28. Targeting CD28 prevents T-cell exhaustion and apoptosis.

Experimental application of the tri-specific antibody led to T cell-mediated killing of cancer cells in vitro and to suppression of myeloma growth in mice. Safety tests in non-human primates showed a risk of cytokine-release syndrome, which was higher for intravenous than subcutaneous administration.

Germany is making childhood vaccination against measles mandatory

German authorities have passed a law that requires all children of school age to be vaccinated for measles. The coverage in Germany is at 93%, while 95% is necessary for herd immunity and prevention of outbreaks. If parents fail to vaccinate their children, they can be fined up to €2,500, and younger children will be banned from day-care facilities. In addition, staff at kindergartens, schools medical and community facilities must be vaccinated.

Germany thus responds to the global increase in measles incidence, driven mostly by vaccine skepticism. One of the most severe outbreaks is underway in the Pacific island of Samoa, where >1% of the population has been infected and 37 people died. The United Nations has provided Samoa with >100,000 doses of the measles vaccine in response.

Prophylactic pancreatic cancer vaccine extends survival in a preclinical study

A personalized cell-based cancer vaccine delayed disease onset and progression in a mouse model of pancreatic cancer.⁷ The vaccine consists of pluripotent stem cells engineered to harbor tumor-associated mutations in KRAS and p53 and infected with replicating oncolytic Adenovirus and Vaccinia virus. When infused back into the mouse in an individualized fashion, the cells induced tumor-specific T-cell responses and doubled survival.

“This is preliminary data from tests on mice but it could be a platform for developing personalized and powerful cancer vaccines to reduce cancer incidence in at-risk individuals,” senior author Yaohe Wang of Queen Mary University of London said.

High-dose quadrivalent influenza vaccine for the elderly approved in the U.S

FDA has approved the Fluzone High-Dose quadrivalent influenza vaccine (Sanofi) for use in adults 65 years of age and older. It targets two strains of each influenza A and B, one B strain more than the trivalent version of the vaccine, which has been in use since 2009. The decision was based on Phase 3 data showing superior immunogenicity compared to two different trivalent formulations.

Due to the weakening of the immune system in the elderly, high-dose vaccines have proved more efficient in preventing influenza in this age group.

Polio vaccine causes more infections than the wild virus

Poliovirus strains derived from vaccines were responsible for 195 cases in 2019, compared to 113 cases caused by the wild strains. The data released by the World Health Organization are from January to November. The numbers were 104 and 33, respectively, for 2018.

The attenuated vaccine virus occasionally mutates and reverts to being infectious and causing disease. Outbreaks of vaccine-derived polio are caused by type 2 virus, which was eliminated in 1999. This strain has not been used in vaccines since 2016, but it remains in circulation.

Poliomyelitis affects the nervous system, mostly in children under the age of 5, and can lead to complete paralysis. Global burden of the disease has decreased by 99% in the last three decades from 350,000 annual cases.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.