9vHPV vaccine offers long-lasting protection from cancer
The 9-valent HPV vaccine (Gardasil 9, Merck) protected against > 90% of cervical, vulvar and vaginal cancer cases six years after the first dose.Citation1 The randomized double-blind Phase 3 trial, which enrolled > 14,000 female subjects aged 16–26, found persistent antibody responses against all nine HPV strains five years after vaccination. The participants will be followed for additional 10 years.
The nine strains targeted by the vaccine cause 90% of cervical cancers and genital warts. Although the immunization rates are on the rise in the US, the Centers for Disease Control and Prevention (CDC) estimated that only ∼40% of teens complete the schedule.
- Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, Mayrand MH, Ruiz-Sternberg AM, Stapleton JT, Wiley DJ, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Cuzick J, Garland SM, Kjaer SK, Bautista OM, Haupt R, Moeller E, Ritter M, Roberts CC, Shields C, Luxembourg A. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial. Lancet 2017; doi: 10.1016/S0140-6736(17)31821-4.
CAR-T therapy approved for non-Hodgkin's lymphoma
The US Food and Drug Administration (FDA) has approved Axicabtagene ciloleucel (Yescarta, Gilead Sciences) for treatment of diffuse large B cell lymphoma. Axicabtagene ciloleucel is a form of CAR-T cell therapy in which patients' T lymphocytes are harvested and genetically engineered to target the CD19 antigen found on lymphoma cells.
The approval is based on 2-year results of the ZUMA-1 trial, in which 80% of patients, including many who had relapsed several times after chemotherapy or bone-marrow transplants, responded to treatment and 44% went into remission with a median follow-up of 9 months.
The shingles vaccine Shingrix has been approved in US and Canada
The varicella zoster virus vaccine Shingrix (GSK) has been approved for the prevention of shingles in US and Canada for people aged ≥50 years. The CDC endorsed Shingrix over Zostavax (Merck), the zoster vaccine currently in use. The two-dose recombinant, adjuvanted vaccine Shingrix has shown >90% efficacy, compared with ∼50% protection by Zostavax.
Around one-third of people are affected by shingles, which is caused by reactivation of the varicella zoster virus contracted earlier in life. Shingles, which affects predominantly the elderly population, is characterized by a painful rash and can lead to complications such as postherpetic neuralgia.
Development of Ebola vaccines
Two Ebola vaccine candidates proved immunogenic for at least a year. The Phase 2 study enrolled 1,500 people in Liberia and investigated the cAd3-EBOZ (GSK) and rVSV-ZEBOV (Merck) vaccines compared to placebo. Antibody responses at one year were detected in 64%, 80% and 7% of participants, respectively.Citation1
Another vaccine, the recombinant adenovirus-vectored Ad5-EBOV, has been approved in China based on the results of a 500-participant Phase 2 trial in Sierra Leone. Ad5-EBOV is the only vaccine targeting the Ebola strain from the recent epidemic in West Africa.
- Kennedy SB, Bolay F, Kieh M, Grandits G, Badio M, Ballou R, Eckes R, Feinberg M, Follmann D, Grund B, Gupta S, Hensley L, Higgs E, Janosko K, Johnson M, Kateh F, Logue J, Marchand J, Monath T, Nason M, Nyenswah T, Roman F, Stavale E, Wolfson J, Neaton JD, Lane HC; PREVAIL I Study Group. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017;377(15):1438–1447.
Typhoid fever vaccine was endorsed by WHO for use in young children
The World Health Organization's Strategic Advisory Group of Experts has recommended the typhoid fever vaccine Typbar-TCV (Bharat Biotech) for use in children aged <2 years. It also suggested catch-up vaccinations for children under 15 years old. Typbar-TCV is thus the first typhoid fever vaccine recommended for infants.
The decision is based on a Phase 2 challenge study involving >100 healthy adults, in which the vaccine halved the number of infections compared to placebo and performed equally well as the licensed typhoid fever vaccine Typhim Vi (Sanofi).Citation1
Salmonella typhi infects >20 million people annually. The infection is fatal for ∼1% of those infected.
- Jin C, Gibani MM, Moore M, Juel HB, Jones E, Meiring J, Harris V, Gardner J, Nebykova A, Kerridge SA, Hill J, Thomaides-Brears H, Blohmke CJ, Yu LM, Angus B, Pollard AJ. Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial.
Third dose of mumps vaccine should be given during outbreaks, according to CDC
The CDC expert committee has recommended a third dose of mumps vaccine for at-risk people as a means to fight mumps outbreaks. While the two-dose MMR vaccine is effective, immunity to mumps wanes over time. The third dose had effectiveness of >60% and an excellent safety profile in a large-scale clinical trial. There have been 150 mumps outbreaks in the US alone since January 2016.
Success of checkpoint immunotherapy might depend on the composition of gut microbiota
Two studies suggest that gut microbes might influence the response to PD-1-blocking immunotherapy. In the first one, researchers collected fecal samples from melanoma patients before enrollment for checkpoint inhibition treatment. They found that the response was positively correlated with the diversity of species in the gut flora as well as the presence of Ruminococcaceae.Citation1 In addition, fecal transplants from responding patients to germ-free mice increased their anti-tumor immunity.
In the second study, treatment with antibiotics prior to PD-1 immunotherapy was found to negatively correlate with lung or urothelial cancer patients' response.Citation2 Akkermansia bacteria were found in responders' stool, and their oral supplementation in a mouse model improved the outcome of immunotherapy.
- Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Sloane RS, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Sanchez EMR, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 2017; doi: 10.1126/science.aan4236.
- Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 2017; doi: 10.1126/science.aan3706.
Universal influenza vaccine enters Phase 2 clinical trial
A universal influenza vaccine (Vaccitech) enrolled first 500 subjects ≥65 years old for a Phase 2 study in UK. The candidate will be compared to placebo and an existing influenza vaccine. The candidate has been safe and elicited T-cell responses in five small-scale trials.
Unlike traditional vaccines which target fast evolving surface antigens, this universal vaccine is directed against the conserved nucleoprotein and Matrix Protein 1.
Zika vaccine proved safe and immunogenic in early trial
The synthetic DNA vaccine against Zika infection GLS-5700 (Inovio and GeneOne) elicited antibody responses in 80% of tested volunteers. In the dose-escalating Phase 1 trial 40 subjects received up to three intradermal doses with subsequent electroporation.Citation1 No serious adverse events were reported.
Earlier trials showed GLS-5700 was 100% efficacious in mice and non-human primates in preventing Zika infection. The vaccine has good temperature stability, which might be important in potential future Zika outbreaks.
- Tebas P, Roberts CC, Muthumani K, Reuschel EL, Kudchodkar SB, Zaidi FI, White S, Khan AS, Racine T, Choi H, Boyer J, Park YK, Trottier S, Remigio C, Krieger D, Spruill SE, Bagarazzi M, Kobinger GP, Weiner DB, Maslow JN. Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine – Preliminary Report. N Engl J Med. 2017; doi: 10.1056/NEJMoa1708120.
Peanut allergy vaccine failed Phase 3 trial
The peanut allergy vaccine Viaskin Peanut (DBV Technologies) outperformed placebo in a 350-patient Phase 3 PEPITES study, but not enough as to warrant approval by the FDA. 35% of children aged 4–11 in the experimental group were sensitized after one year, compared to 14% in the placebo group.
The Viaskin patch is a wearable platform for epicutaneous delivery of small amounts of peanut proteins. The trial participants received daily doses of 250 μg.
New pneumococcal vaccine elicits wide protection in mice
Immune responses to 72 pneumococcal strains were elicited by a new vaccine in a preclinical study.Citation1 In contrast to PCVs, in which pneumococcal polysaccharides are covalently conjugated to proteins, the new vaccine contains pneumococcal polysaccharides encapsulated in a liposome, which allows non-covalent attachment of the carrier proteins.
“The advantage of our approach is that we don't have to apply the more complex covalent chemistry that is required for [PCV],” senior author Blaine Pfeifer said. “As a result, we can extend beyond the 13 types of sugars, potentially providing universal coverage against bacteria that cause pneumonia, meningitis, sepsis and other types of pneumococcal disease.”
- Jones CH, Zhang G, Nayerhoda R, Beitelshees M, Hill A, Rostami P, Li Y, Davidson BA, Knight P 3rd, Pfeifer BA. Comprehensive vaccine design for commensal disease progression. Sci Adv 2017;3(10):e1701797.