Human Vaccines & Immunotherapeutics: News

Vaccination with the 4-valent HPV vaccine (Gardasil, Merck) offers at least 10-year protection against infection. Among >1,600 children of both sexes immunized at 9–15 years of age, ≥90% were seropositive against three HPV strains (6, 11 and 16) 10 years later.¹ The titers were higher if the vaccine had been administered earlier in life. While 10 subjects reported infection persisting ≥6 months, none developed any HPV-related disease.

The vaccine might also prevent a rare childhood respiratory disease, juvenile-onset recurrent respiratory papillomatosis (JORRP), which is caused by HPV strains 6 and 11.² A prospective study followed Australian surveillance program for monitoring pediatric diseases, and found that the incidence of JORRP has declined following the implementation of a national HPV vaccination program. The chronic disease is transmitted from an HPV-infected mother to child around the time of birth. None of the mothers of children diagnosed with JORRP between 2012 and 2016 was vaccinated against HPV.

Early trial shows pembrolizumab is effective against rare pregnancy-associated cancer

Three out of four patients with a cancerous form of gestational trophoblastic disease (GTD) went into remission after treatment the PD-1-targeting MAb pembrolizumab.¹ GTD, which affects 18,000 women globally each year, involves abnormal growth of trophoblasts that form the placenta in pregnant women. It is typically associated with high PD-L1 levels.

“We have been able to show for the first time that immunotherapy may be used to cure patients of cancerous GTD. The current treatments to tackle GTD cure most cases of the disease. However, there are a small number of women whose cancers are resistant to conventional therapies, and as a result have a fatal outcome. Immunotherapy may be a life-saving treatment and can be used as an alternative to the much more toxic high dose chemotherapy that is currently used,” senior author Michael Seckl of Imperial College London said.

New developments in dengue vaccines

The tetravalent dengue vaccine candidate TAK-003 (Takeda) has shown sustained antibody responses against all four dengue strains.¹ Interim data of a randomized, placebo-controlled Phase 2 clinical trial, which enrolled almost 1,800 subjects aged 2–17 years in three endemic countries, were collected at 18 months post-vaccination, and the trial will continue for another 30 months.

The only licensed dengue vaccine, Dengvaxia (Sanofi), was found to worsen subsequent infection in individuals previously unexposed to the virus. The second infection by dengue typically has more serious symptoms than the first, and immunization behaves like natural infection in dengue-naïve individuals. The company has requested a label change that will result in fewer eligible recipients of the vaccine.

Cell-based immunotherapy successfully treated type 1 diabetes in mice

Hematopoietic stem and progenitor cells (HSPCs) have been found deficient in the expression of the checkpoint ligand PD-L1 in mice and humans suffering from type 1 diabetes.¹ The study sought to ameliorate the defect by harvesting HSPCs from non-obese diabetic mice and genetically engineer or pharmacologically modulate them to overexpress PD-L1. The modified HSPCs were able to revert diabetes in experimental mouse model with 30% of animals remaining diabetes-free their entire lives.

In type 1 diabetes, autoreactive T cells attack pancreatic islet cells that produce insulin, and the PD-1 checkpoint pathway normally inhibits hyper-reactive T cells. “Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired,” senior author Paolo Fiorina of Harvard Medical School said. “We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease.”

Third recombinant hepatitis B vaccine approved by FDA

The US Food and Drug Administration (FDA) has approved the hepatitis B vaccine Heplisav-B (Dynavax) for adults. The vaccine, which was previously rejected twice, should be ready for commercial distribution in 1Q of 2018. The decision is based on clinical trial data showing higher and earlier protection of the vaccine than one of two licensed vaccines, Engerix-B.

Heplisav-B is administered in two doses one month apart, compared to Engerix-B's three-dose regimen at 0-1-6 months. The overall rate of adverse events was low for Heplisav-B.

Bivalent CAR-T cell therapy trial started in US

The Seattle Children's Hospital has opened a CAR-T cell immunotherapy trial (PLAT-05) for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia (ALL). The treatment simultaneously targets two antigens, CD19 and CD22, which are expressed by B lymphocytes.

“In launching a bilateral attack on the cancer cells, we hope this trial will help us develop a T-cell therapy that leads to long-term remission for many more of our patients,” lead investigator Rebecca Gardner said in a press release.

The procedure involves harvesting patient's T cells and genetically engineering them to recognize an antigen overexpressed on cancer cells. In 2017, the FDA approved monovalent CAR-T cell immunotherapy targeting CD19 for children with ALL.

A mosaic HIV vaccine is tested in Africa

A clinical trial in South Africa will investigate a 4-valent ‘mosaic’ HIV vaccine in 2,600 HIV-negative women. In the Phase 2b Imbokodo study, participants will receive four doses of the vaccine or placebo, the last two doses will be administered together with the HIV protein gp140 and aluminum adjuvant.

The so-called mosaic vaccine consists of immunogens from a variety of HIV strains and thus should provide a broad protection.

Follow-up study will investigate RSV vaccine's long-term effect

The RSV vaccine candidate MVA-BN RSV elicits specific antibodies lasting for at least six months in a Phase 2 trial from 2016. Now an extension study will re-enroll 20% of the original >400 participants, who will receive a low or a high dose of a booster injection. The objective is to determine if the vaccine has an effect over multiple seasons or if it has to be given annually.

MVA-BN RSV consists of five different RSV immunogens. It has been shown to elicit both T-cell and antibody responses.

Zika vaccine candidate advances to clinical trials

The Zika vaccine TAK-426 (Takeda) has entered a Phase 1 study with 240 flavivirus-naïve healthy adults. Researchers will determine safety and immunogenicity of the vaccine. No pregnant women will be admitted into the study.

TAK-426, which is the 5th Zika vaccine to advance into human trials, is a purified, inactivated, whole-virus vaccine administered in a two-dose regimen with an aluminum adjuvant.

Influenza vaccine candidate offers broad protection in mice

An adenovirus-vectored influenza vaccine derived from ancestral genes of four viral clades protected animals in a preclinical challenge study.¹ Mice that received the candidate survived infection with the H1N1, H3N1, H3N2 and H5N1 strains, with higher doses completely preventing disease symptoms. In contrast, animals immunized with a traditional nasal-spray vaccine died of the infection.

The hope of the research is to get a step closer towards a universal influenza vaccine, which would provide a life-long protection. “Our current influenza vaccine programs and technologies reduce influenza infections and hospitalizations by 4.75 percent and 6.9 percent, respectively,” senior author Eric Weaver of University of Nebraska said. “There is no doubt that there is a need for more effective vaccine technologies.”