HPV vaccine might help reduce rate of head-and-neck cancers, according to study
An 88% drop in oral HPV infections was observed in a population immunized with Gardasil (Merck). The study investigated data on >2,600 adults aged 18-33 from the US National Health and Nutrition Examination Survey in the period 2011-4, and compared the prevalence of oral infections relative to HPV vaccination status.
Consequently, the vaccine might prevent head-and-neck cancers, an indication for which it has not yet been approved. The benefit was observed especially in males, which is relevant because HPV-related head and neck cancers disproportionately affect men.
“When we compared the prevalence in vaccinated men to non-vaccinated men, we didn't detect any infections in vaccinated men. The data suggests that the vaccine may be reducing the prevalence of those infections by as high as 100 percent,” lead investigator Maura Gillison of MD Anderson Cancer Center said in a release.
Anti-PD-L1 immunotherapy beneficial in NSCLC condition even after disease progressed
Continued treatment with the anti-PDL-1 checkpoint inhibitor atezolizumab (Tecentriq, Roche) shrank tumors despite initial progression. According to an update on a Phase 2 trial involving patients with previously treated advanced or metastatic non-small-cell lung cancer (NSCLC), 82% of 61 subjects who continued atezolizumab therapy after tumor progression saw subsequent stabilization or shrinkage.
“We found that there was a benefit for some patients continuing with the drug even after a CT scan suggested progressive disease. Atezolizumab can control lung cancer for a longer period of time than was initially thought,” said co-author Angel Artal-Cortes of University Hospital Miguel Servet, Zaragoza, Spain.
Positive early clinical results for a new mRNA vaccine technology
The lipid nanoparticle-formulated mRNA influenza vaccines mRNA-1440 and mRNA-1851 (Moderna) were immunogenic in preclinical and early clinical trials.Citation1 These vaccines encode hemagglutinin proteins from H10N8 (mRNA-1440) and H7N9 (mRNA-1851) avian influenza strains.
A single dose of mRNA-1851 protected mice from lethal challenge, while mRNA-1440 induced 100% seroconversion rate in 23 subjects enrolled for a first-in-human Phase 1 study. Moderna has 12 mRNA candidates against viral diseases and cancer in development. The mRNA technology uses intramuscular delivery without the need for electroporation, which can be painful.
- Bahl K, Senn JJ, Yuzhakov O, Bulychev A, Brito LA, Hassett KJ, Laska ME, Smith M, Almarsson Ö, Thompson J, Ribeiro AM, Watson M, Zaks T, Ciaramella G. Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses. Mol Ther 2017; doi: 10.1016/j.ymthe.2017.03.035
Pembrolizumab combination approved in the US for advanced lung cancer
The US Food and Drug Administration (FDA) has approved the anti-PD-1 checkpoint inhibitor pembrolizumab (Keytruda, Merck) in combination with chemotherapy for previously untreated advanced non-squamous NSCLC. The accelerated decision was based on positive results from a study of 123 patients with metastatic NSCLC.
Pembrolizumab had been approved as first-line monotherapy in NSCLC patients with high levels of PD-L1 ligand, which account for ∼30% of cases. The current approval comprises ∼75% of lung cancer cases.
Vaccine against weakly immunogenic antigens inhibits HIV replication in preclinical models
A mucosal adenovirus-vectored vaccine containing the weak SIV antigens tat, vif, rev and vpr fused to MHC class II reduced viremia and inhibited early viral replication in a macaque challenge model.Citation1 Two out of six tested animals had undetectable long-term viremia.
In contrast to traditional vaccine candidates, weak immunogens should not overwhelm the immune system, and the immune response might last longer. “We're presenting an entirely new vaccine solution. Our vaccine supports the work of the immune system in developing an effective combating mechanism against the virus, rather than immediately combating the toughest parts of the virus. In combination with other vaccines, this approach can prove to have a highly efficient effect,” senior author Peter Holst told the press.
- Xu H, Andersson AM, Ragonnaud E, Boilesen D, Tolver A, Jensen BAH, Blanchard JL, Nicosia A, Folgori A, Colloca S, Cortese R, Thomsen AR, Christensen JP, Veazey RS, Holst PJ. Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication. EBioMedicine 2017; 18:204–215
Phase IV data confirm prostate cancer vaccine sipuleucel-T's potential
Clinical data on 1,900 patients with metastatic castration-resistant prostate cancer, who received sipuleucel-T immunotherapy (Provenge, Dendreon), were in line with results that secured FDA approval in 2010 for this vaccine. It also has been shown that African Americans benefit most with median survival of 37 months compared to 28 months in Caucasians. Prostate cancer is 60% more prevalent among African Americans.
Sipuleucel-T is an autologous cell therapy primed with prostatic acid phosphatase antigen, which is present in 95% of prostate cancers, and GM-CSF adjuvant.
12 childhood vaccines become mandatory in Italy
Parents in Italy are now required by law to vaccinate their children against measles, mumps, rubella, varicella, meningococcus B and C, polio, diphtheria, tetanus, hepatitis B, pertussis, and Haemophilus influenzae type b. Without immunization, young children will not be eligible for nursery school and parents may be punished by fines.
“The lack of appropriate measures over the years and the spread of anti-scientific theories, especially in recent months, has brought about a reduction in protection,” Italian Prime Minister Paolo Gentiloni told the media. Italy has reported >2,000 measles cases this year, compared to 840 in the year of 2016 and 250 in 2015.
DNA HIV vaccine candidate proved immunogenic in early tests
The experimental HIV vaccine Pennvax-GP (Inovio) elicited CD4+ and CD8+ T-cell responses in 93% of 76 vaccinated people in a placebo-controlled early stage of HVTN 098 clinical trial. In addition, 94% of evaluated subjects developed antibody responses. Intradermal and intramuscular routes yielded comparable results.
Pennvax-GP is a DNA vaccine encoding the env, gag and pol antigens of HIV-1 which is administered with the immune-activating cytokine IL-12.
Ebola vaccine will be used for the first time
The Democratic Republic of Congo has approved the use of rVSV-ZEBOV vaccine (Merck) to fight an emerging Ebola outbreak in the northeast of the country. Although the vaccine has not been licensed, it has demonstrated a high protection rate in clinical trials.
The outbreak has killed four people with >50 suspected cases. The vaccine will be offered to people who were in contact with those affected, and to healthcare and field workers.
New Zika vaccine candidate provided protection in preclinical trial
A VLP vaccine against the mosquito-borne Zika virus elicited high titers of neutralizing antibodies in mouse models.Citation1 The vaccine, which is generated by co-expressing structural (CprME) and non-structural (NS2B/NS3) Zika proteins that self-assemble in suspension of mammalian cells, was administered along with the AddaVax adjuvant.
- Boigard H, Alimova A, Martin GR, Katz A, Gottlieb P, Galarza JM. Zika virus-like particle (VLP) based vaccine. PLoS Negl Trop Dis 2017; 11(5):e0005608
Novel malaria vaccine efficacious in a monkey challenge model
A malaria vaccine candidate protected Aotus monkeys from a virulent Plasmodium falciparum infection.Citation1 The vaccine contains the AMA1-RON2L complex, which the parasite uses to attach to red blood cells. Compared to another vaccine in development, which targets the AMA1 component alone and delayed infection in 1 of 8 animals, the new vaccine completely protected 4 and delayed infection in 3 of 8 animals. The overall antibody levels did not differ between the two groups.
- Srinivasan P, Baldeviano GC, Miura K, Diouf A, Ventocilla JA, Leiva KP, Lugo-Roman L, Lucas C, Orr-Gonzalez S, Zhu D, Villasante E, Soisson L, Narum DL, Pierce SK, Long CA, Diggs C, Duffy PE, Lescano AG, Miller LH. A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection. npj. Vaccines 2017; doi: 10.1038/s41541-017-0015-7