Catch-up HPV vaccination is effective in female adolescents
Vaccination with the 4-valent HPV vaccine prevents pre-cancerous cervical intraepithelial neoplasia in women 14–20 years old who were not vaccinated at the recommended age of 11–12 years.1 This population-based case-cohort study of > 25,000 US subjects found strongest protection in women who received all three doses and did not report a significant protection in women aged ≥ 21 years.
“In comparison to other countries, HPV vaccine uptake in the US has been relatively low. Our findings show that girls and women who did not receive the full vaccine series at age 11–12 can still benefit from significant protection if they receive the full three doses of vaccine by the age of 20. The evidence suggests that protection is strongest the earlier the vaccine is initiated, and after the age of 21, the evidence of effectiveness is unclear. Further research in other settings, and using the recently introduced nonavalent vaccine, will now be needed to assess the effectiveness of vaccinating women aged 21–26 years,” lead author Michael Silverberg of Kaiser Permanente in Oakland said.
1. Silverberg MJ, Leyden WA, Lam JO, Gregorich SE, Huchko MJ, Kulasingam S, Kuppermann M, Smith-McCune KK, Sawaya GF. Effectiveness of catch-up human papillomavirus vaccination on incident cervical neoplasia in a US health-care setting: a population-based case-control study. Lancet Child Adolesc Health 2018; doi: 10.1016/S2352-4642(18)30220-7
Clinical trial investigates the potential of CAR-T therapy of pediatric solid tumors
Children with recurrent sarcoma, kidney and brain cancers are enrolled in the STRIvE-01 study of CAR-T treatment, in which patients’ own T-cells are genetically engineered to recognize a mutated or overexpressed EGFR receptor common in many cancer types.
While the CAR-T method has been successfully used in blood cancers and approved for the treatment of B-cell lymphoma, it has seen only limited progress in solid tumors.
Rotavirus vaccine prevents one-third of infant deaths from diarrhea in Malawi
Children in Malawi vaccinated with the monovalent rotavirus vaccine (RV1) had a 34% lower risk of death from diarrhea.1 The population-based birth cohort study included almost 50,000 subjects born after Malawi introduced RV1 in 2002. Vaccine coverage in the country reached 90% within a year.
“Rotavirus remains a leading cause of severe diarrhea and death among infants and young children in many countries in Africa and Asia. Our findings strongly advocate for the incorporation of rotavirus vaccine into the childhood immunisation programmes of countries with high rates of diarrhea deaths, and support continued use in such countries where a vaccine has been introduced,” senior author Nigel Cunliffe of University of Liverpool said.
1. Bar-Zeev N, King C, Phiri T, Beard J, Mvula H, Crampin AC, Heinsbroek E, Lewycka S, Tate JE, Parashar UD, Costello A, Mwansambo C, Heyderman RS, French N, Cunliffe NA; VacSurv Consortium. Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort. Lancet Glob Health 2018; doi: 10.1016/S2214-109X(18)30314-0
Progress in predictive biomarkers for checkpoint immunotherapy
Overall survival was predicted by analysis of CT scans of cancer patients enrolled in clinical trials evaluating immune checkpoint PD-1 pathway blockade.1 Researchers used machine-learning techniques to extract information from a database of CT scans matched to tumor genomes, which resulted in a ‘radiomic score’. They found that higher scores correlated with the response to, and the success of, the PD-1-targeting immunotherapy.
In another study, scientists analyzed gene expression patterns in cases of spontaneous tumor regression, arguing that underlying immune mechanisms might predict response to immunotherapy. Based on these patterns, they applied an Immuno-Predictive Score (IMPRES) to published samples of 300 melanoma patients undergoing PD-1 or CTLA-4 blockade. IMPRES correctly identified almost all subjects who responded to treatment and half of those who did not.
1. Sun R, Limkin EJ, Vakalopoulou M, Dercle L, Champiat S, Han SR, Verlingue L, Brandao D, Lancia A, Ammari S, Hollebecque A, Scoazec JY, Marabelle A, Massard C, Soria JC, Robert C, Paragios N, Deutsch E, Ferté C. A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study. Lancet Oncol 2018; doi: 10.1016/S1470-2045(18)30413-3
2. Auslander N, Zhang G, Lee JS, Frederick DT, Miao B, Moll T, Tian T, Wei Z, Madan S, Sullivan RJ, Boland G, Flaherty K, Herlyn M, Ruppin E. Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma. Nat Med 2018; doi: 10.1038/s41591-018–0157-9
Congo fights second Ebola outbreak in short succession
Another Ebola outbreak was declared in the Democratic Republic of Congo just days after the first one had been contained. Several dozen cases have likely been caused by the Ebola Zaire strain according to the World Health Organization (WHO). The experimental vaccine rVSV-ZEBOV (Merck) will be distributed, as was done for the previous outbreak.
“Here we are responding to an outbreak of a high-threat pathogen with one of the highest mortality rates of any known diseases, but in the context of a war zone,” Peter Salama of WHO said. “We are at the top of the degree of difficulty scale.”
Combination of anti-PD-1 and TLR agonist treatment promising in aggressive melanoma
The PD-1-specific MAb pembrolizumab (Keytruda, Merck) together with the TLR9 agonist SD-101 showed a 12-month progression-free survival of almost 90% in nine patients with unresectable or metastatic malignant melanoma. Two of the subjects, enrolled in a Phase 1b study, had a complete remission.1
SD-101 is a DC-stimulating, synthetic CpG oligonucleotide, which changes the tumor microenvironment in a way that boosts both innate and adaptive immunity. Researchers hope that it might enable the use of checkpoint inhibitors in patients otherwise unresponsive to the treatment.
1. Ribas A, Medina T, Kummar S, Amin A, Kalbasi A, Drabick JJ, Barve M, Daniels GA, Wong DJ, Schmidt EV, Candia AF, Coffman RL, Leung ACF, Janssen RS. SD-101 in Combination with Pembrolizumab in Advanced Melanoma: Results of a Phase 1b, Multicenter Study. Cancer Discov 2018; doi: 10.1158/2159-8290.CD-18-0280
New developments in universal influenza vaccine research
The universal influenza vaccine candidate M-001 (BiondVax) is tested in a randomized, double-blind, placebo-controlled Phase 3 trial involving 10,000 adults aged ≥ 65 years. The study will investigate protection from influenza and reduction of disease severity. M-001, which consists of a mixture of conserved peptides, is administered in two doses three weeks apart.
Another investigational universal influenza vaccine elicited strong antibody responses in preclinical models with protection from viral challenge.1 The mRNA vaccine, which is formulated in lipid nanoparticles, encodes a full-length hemagglutinin. However, unlike traditional seasonal vaccines, it elicits antibodies targeting the conserved stalk region of the surface molecule.
1. Pardi N, Parkhouse K, Kirkpatrick E, McMahon M, Zost SJ, Mui BL, Tam YK, Karikó K, Barbosa CJ, Madden TD, Hope MJ, Krammer F, Hensley SE, Weissman D. Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nat Commun 2018; doi: 10.1038/s41467-018-05482-0
New vaccine reduces acne in a preclinical study
Vaccination with the Propionibacterium acnes toxin CAMP reduced bacterial growth and inflammatory response in a mouse model of the inflammatory disease of the skin.1 In addition, CAMP-targeting antibodies reduced the pro-inflammatory cytokines IL-8 and IL-1β in ex vivo human acne lesions. It is the first time that the pore-forming CAMP toxin has been implicated in the pathogenesis of acne.
“Current treatment options are often not effective or tolerable for many of the 85 percent of adolescents and more than 40 million adults in the United States who suffer from this multi-factorial cutaneous inflammatory condition. New, safe, and efficient therapies are sorely needed,” senior author Chun-Ming Huang of University of California in Sand Diego said.
1. Wang Y, Hata TR, Tong YL, Kao MS, Zouboulis CC, Gallo RL, Huang CM. The Anti-Inflammatory Activities of Propionibacterium acnes CAMP Factor-Targeted Acne Vaccines. J Invest Dermatol 2018; doi: 10.1016/j.jid.2018.05.032
HPV vaccination rate has increased slightly in the US
The initiation and completion rates of the recommended HPV vaccination regimen were 66% and 49%, respectively, for US adolescents in 2017. According to the Centers for Disease Control and Prevention (CDC), these numbers increased by ~ 5% from 2016. Vaccination coverage was lower in rural areas, and boys had a lower rate of uptake than girls. CDC officials are targeting 80% coverage by 2020.
Responses to rotavirus vaccination might be affected by the gut microbiota
Antibiotics increase the immunogenicity of rotavirus vaccination, a proof-of-concept study in healthy adults showed.1 Subjects treated with broad – or narrow-spectrum antibiotics had a higher rate of viral shedding after vaccination compared to untreated control group. The rate of fecal shedding correlates with vaccine-induced protection.
“All microbiota in the gut, including bacteria, fungi, and viruses, have evolved together for so long, it is very likely viruses exploit bacteria or immune responses in the gut to their advantage. Perhaps certain bacteria help the rotavirus replicate or antibiotics alter bacteria and thereby trigger immune responses that are favorable or unfavorable for a virus,” lead author Vanessa Harris of University of Amsterdam said.
1. Harris VC, Haak BW, Handley SA, Jiang B, Velasquez DE, Hykes BL Jr, Droit L, Berbers GAM, Kemper EM, van Leeuwen EMM, Boele van Hensbroek M, Wiersinga WJ. Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial. Cell Host Microbe 2018; 24(2):197–207.e4
Therapeutic HIV vaccine is tested in an early trial
A randomized, double-blind, placebo-controlled Phase 1/2 study has enrolled 45 patients with chronic HIV infection to assess the potential of the DNA vaccine PENNVAX-GP (Inovio) to induce remission and control of the virus. The vaccine, which previously elicited durable and robust immune responses in healthy volunteers, targets the Gag, Pol and Env antigens of all major HIV strains.
Subjects will receive PENNVAX-GP along with a plasmid encoding the immune activator IL-12 (INO-9012) four times four weeks apart. Safety, tolerability and immunogenicity will also be monitored.
“Although we do not expect this or any vaccine to be curative on its own, we firmly believe that a therapeutic vaccine will likely be needed as part of a combination approach,” principal investigator Steven Deeks of University of California in San Francisco said.