Advanced search
Publication Cover
Human Vaccines & Immunotherapeutics Volume 12, 2016 - Issue 8
Submit an article Journal homepage
350
Views
0
CrossRef citations to date
0
Altmetric
News, Policy & Profiles

Human Vaccines & Immunotherapeutics: News

Pages 1950-1951 | Published online: 12 Aug 2016

‘Universal’ cancer vaccine promising in early testing

A new approach to neoantigen delivery could lead to vaccination against many types of cancers. In a study published in Nature,1 the researchers injected RNA-liposome complexes into the blood, and directed them to dendritic cells (DCs) by adjusting the net charge. The RNA encoded cancer neoantigens that were presented by DCs in various lymphoid compartments.

The vaccine induced tumor rejection in mice. Preliminary clinical data from three melanoma patients suggest that the vaccine elicits strong interferon-α and T-cell responses. A dose-escalation Phase 1 study is underway. This fast and inexpensive method might prove suitable for delivery of many antigens for presentation to DCs.

  1. Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, Grunwitz C, Vormehr M, Hüsemann Y, Selmi A, Kuhn AN, Buck J, Derhovanessian E, Rae R, Attig S, Diekmann J, Jabulowsky RA, Heesch S, Hassel J, Langguth P, Grabbe S, Huber C, Türeci Ö, Sahin U. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 2016; 534(7607):396-401

The first cholera vaccine approved in the U.S.

Vaxchora cholera vaccine (PaxVax) has been licensed by the U.S. Food and Drug Administration (FDA). It becomes the first cholera vaccine available to American travelers, and the only single-dose cholera vaccine worldwide.

Vaxchora is an oral live attenuated vaccine, which showed efficacy of 90% at 10 days and 80% at 90 days after vaccination. The U.S. Centers for Disease Control and Prevention (CDC) recommended the use of Vaxchora for adults aged 18–64 traveling to cholera-endemic regions.

Pembrolizumab better than chemotherapy in NSCLC patients

The checkpoint inhibitor MAb pembrolizumab (Keytruda, Merck) improved survival as a first-line therapy in patients with high-PD-L1 non-small cell lung cancer (NSCLC). In the Phase 3 Keynote024 trial, subjects who received pembrolizumab had higher progression-free survival and overall survival than patients treated with chemotherapy. The Data-Monitoring Committee has recommended to stop the study and to offer the immunotherapeutic to the latter group of patients as well.

Pembrolizumab is approved as a second-line therapy of metastatic NSCLC in patients who failed prior chemotherapy. It works by blocking the PD-1 pathway, which is exploited by some cancers to inhibit the natural anti-tumor immune reaction.

HPV vaccination has had a major impact on disease incidence, study finds

In countries with high vaccination coverage, the implementation of vaccination with the quadrivalent HPV vaccine (Gardasil, Merck) led to a 90% decrease in HPV incidence. According to a study published in Clinical Infectious Diseases,1 the effect was accompanied by a 90% decrease in genital warts and high-grade cervical abnormalities.

At the same time, the researchers warned that vaccine uptake varies over a wide range. According to the CDC, only 40% of U.S. girls and 21% of boys were immunized against HPV. The virus thus remains a significant cause of morbidity.

  1. Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, Lindsay BR, Kuter BJ, Perez G, Dominiak-Felden G, Saah AJ, Drury R, Das R, Velicer C. Impact and Effectiveness Of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of Ten Years of Real-World Experience. Clin Infect Dis 2016; doi: 10.1093/cid/ciw354

Combination of chemo- and immunotherapy promising for colorectal cancer patients

In an early trial involving 23 patients with metastatic colorectal cancer, atezolizumab (MPDL3280A, Roche) administered together with the MEK inhibitor cobimetinib led to tumor shrinkage in 17% of the subjects and to stable disease in 22%. Atezolizumab is a PD-L1 inhibitor, and baseline PD-L1 levels did not affect the outcome. No serious adverse events were reported.

The patients had microsatellite instability-low form of the disease, the senior author of the study Johanna Bendell of Tennessee Oncology explains. “So far, immunotherapy has only shown activity in patients with microsatellite instability-high colorectal cancer, which is only 5% of the population. What we saw is consistent with the hypothesized mechanism of action of this combination, which shows promise in giving the other 95% of colon cancer patients a chance to respond to immunotherapy.”

RSV vaccine candidate fast-tracked for older adults

A respiratory syncitial virus (RSV) vaccine RSV F (Novavax) received the FDA fast-track designation for use in adults aged ≥60 years. There is no licensed vaccine against the virus, which kills ∼16,000 elderly annually in the U.S. alone.

In 2014, the candidate was fast-tracked also for maternal immunization of infants. In both groups, Phase 3 trials are underway, with results expected later in 2016.

Immunotherapy of ovarian cancer may benefit from prior chemotherapy

Neoadjuvant chemotherapy administered prior to surgery activates T cells in the ovarian cancer microenvironment, a study published in Clinical Cancer Research found.1The treatment also resulted in higher levels of PD-L1 ligand expression in the tumor, which in turn inhibits the T-cell response. Thus, anti-PD-L1 immunotherapy might benefit from prior neoadjuvant chemotherapy boost.

“Our study suggests that to give patients the best results not only do the immunotherapy drugs need to be given straight after chemotherapy but they also have to able to block PD-L1. Clinical trials are now needed to test this theory. This same approach could also be extended to other kinds of cancer where the same types of chemotherapy are used, such as lung cancer,” senior author Frances Balkwill of Queen Mary University of London said in a press release.

  1. Böhm S, Montfort A, Pearce OM, Topping J, Chakravarty P, Everitt GL, Clear A, McDermott JR, Ennis D, Dowe T, Fitzpatrick A, Brockbank EC, Lawrence AC, Jeyarajah A, Faruqi AZ, McNeish IA, Singh N, Lockley M, Balkwill FR. Neoadjuvant chemotherapy modulates the immune microenvironment in metastases of tubo-ovarian high-grade serous carcinoma. Clin Cancer Res 2016; 22(12):3025-36

First toxic shock syndrome vaccine in clinical testing

The first vaccine against staphylococcal toxic shock syndrome (rTSST-1v) was safe and immunogenic in a Phase 1 trial involving 46 healthy adults. According to a study published in Lancet Infectious Diseases,1 the candidate is a recombinant Staphylococcus aureus toxin mutated in a way that ablates its toxic properties.

The toxic shock syndrome is a rare medical condition caused by S. aureus or group A streptococci and associated with menstruation in young women. Immunocompromised subjects are at particular risk from the syndrome.

  1. Schwameis M, Roppenser B, Firbas C, Gruener CS, Model N, Stich N, Roetzer A, Buchtele N, Jilma B, Eibl MM. Safety, tolerability, and immunogenicity of a recombinant toxic shock syndrome toxin (rTSST)-1 variant vaccine: a randomised, double-blind, adjuvant-controlled, dose escalation first-in-man trial. Lancet Infect Dis 2016; doi: 10.1016/S1473-3099(16)30115-3

CDC did not endorse the FluMist influenza vaccine

U.S. doctors should not administer the FluMist vaccine (AstraZeneca) during the upcoming season, according to the CDC’s Advisory Committee on Immunization Practices. The recommendation is based on three-year data showing that the quadrivalent vaccine was only 3% effective in children aged 2-17 years.

FluMist is a nasal spray—the only influenza vaccine without a need of an injection—making it appealing for parents of young children. The CDC is making effort to ensure sufficient alternative vaccine supply.

Preclinical success for two Zika vaccine candidates

Two vaccines against Zika virus offered complete protection in a mouse challenge model. As described in an article published in Nature,1 one candidate is a plasmid expressing the Zika pre-membrane and envelope immunogens, and the other is a purified inactivated virus. Single injection of either vaccine led to complete protection of mice challenged with the virus 4 and 8 weeks later.

In a second study, scientists isolated antibodies from dengue patients and found that they were able to neutralize Zika virus as well.2 Both dengue and Zika belong to the Flavivirus genus, and the antibodies target conserved surface epitopes. The authors hope the research will lead to the development of a single vaccine against both viruses.

  1. Larocca RA, Abbink P, Peron JP, Zanotto PM, Iampietro MJ, Badamchi-Zadeh A, Boyd M, Ng'ang'a D, Kirilova M, Nityanandam R, Mercado NB, Li Z, Moseley ET, Bricault CA, Borducchi EN, Giglio PB, Jetton D, Neubauer G, Nkolola JP, Maxfield LF, Barrera RA, Jarman RG, Eckels KH, Michael NL, Thomas SJ, Barouch DH. Vaccine protection against Zika virus from Brazil. Nature 2016; doi: 10.1038/nature18952

  2. Barba-Spaeth G, Dejnirattisai W, Rouvinski A, Vaney MC, Medits I, Sharma A, Simon-Lorière E, Sakuntabhai A, Cao-Lormeau VM, Haouz A, England P, Stiasny K, Mongkolsapaya J, Heinz FX, Screaton GR, Rey FA. Structural basis of potent Zika-dengue virus antibody cross-neutralization. Nature 2016; doi: 10.1038/nature18938

Norovirus vaccine candidate enters Phase 2 trial

A norovirus vaccine TAK-214 (Takeda) is being assessed for immunogenicity and efficacy in a Phase 2b study starting in the U.S. The placebo-controlled trial is recruiting several thousand adults aged 18-49 years. TAK-214 is an aluminum-adjuvanted VLP vaccine containing outer-surface proteins from two most common norovirus strains. A Phase 1/2 challenge study showed that the candidate vaccine is generally well-tolerated and had a clinically relevant impact on the symptoms and severity of norovirus illness after challenge.

There is no licensed vaccine against the pathogen, which affects ∼700 million people every year, and is a particular concern in the developing world.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Download PDF

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.