Experts warn of very low influenza vaccine effectiveness this season
Seasonal influenza vaccine might be only ∼10% effective this year, according to a study that analyzed public health records in Australia where the influenza season is already over.1 There were >200,000 influenza cases by mid-October, compared to <60,000 during the 2009 pandemic. Since strains selected for vaccine production in both hemispheres were identical this year, vaccine efficacy is expected to be similar.
According to the US Centers for Disease Control and Prevention, the reason is not a mismatch between the vaccine and circulating strains, but rather antigenic dissimilarity between the A(H3N2) strain in circulation and the egg-produced virus.2 The same discrepancy might also have caused low effectiveness of the last year's vaccine, according to a different study.3
A Public Health England committee concluded that the conventional egg-based vaccine is ineffective for the elderly. As of next season, people aged ≥65 years will receive the adjuvanted influenza vaccine (Fluad, Seqirus).
While the influenza vaccine produced in chicken eggs has been considered potentially hazardous for egg-allergic people, a new report concludes the fear is unwarranted and recommends immunizing all subjects irrespective of the allergy status.4
1.Paules CI, Sullivan SG, Subbarao K, Fauci AS. Chasing Seasonal Influenza — The Need for a Universal Influenza Vaccine. N Engl J Med 2018; 378(1):7-9
2.Dugan VG, Blanton L, Elal AIA, Alabi N, Barnes J, Brammer L, Burns E, Cummings CN, Davis T, Flannery B, Fry AM, Garg S, Garten R, Gubareva L, Jang Y, Kniss K, Kramer N, Lindstrom S, Mustaquim D, O'Halloran A, Olsen SJ, Sessions W, Taylor C, Trock S, Xu X, Wentworth DE, Katz J, Jernigan D. Update: Influenza Activity — United States, October 1–November 25, 2017. MMWR Morb Mortal Wkly Rep 2017; 66(48):1318-1326
3.Zost SJ1, Parkhouse K1, Gumina ME1, Kim K2, Diaz Perez S1, Wilson PC3, Treanor JJ4, Sant AJ5, Cobey S2, Hensley SE6. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A 2017; 114(47):12578-12583
4.Greenhawt M, Turner PJ, Kelso JM. Administration of influenza vaccines to egg allergic recipients: A practice parameter update 2017. Ann Allergy Asthma Immunol 2018; 120(1):49-52
Combination immunotherapy promising for treatment of kidney cancer
The combination of antibodies atezolizumab (Tecentriq, anti-PD-L1) and bevacizumab (Avastin, anti-VEGF, both Roche) improved progression-free survival in inoperable, locally advanced or metastatic renal cell carcinoma patients, compared to the chemotherapy drug sunitinib. The randomized, open-label Phase 3 IMmotion151 study enrolled almost 1,000 participants globally.
The three-way combination of atezolizumab, bevacizumab and chemotherapy was also tested in subjects with previously untreated lung cancer. It reduced the risk of disease progression or death by almost 40% compared to bevacizumab and chemotherapy alone.
Mandatory parental counseling might lead to increased vaccine uptake
Vaccine exemptions dropped by 40% in Washington State after the passing of a 2011 bill that requires parents to discuss vaccine risks and benefits with a healthcare provider.1 The study analyzed public health data in the period 1997–2014 and found an absolute decrease in non-medical exemptions of 3% and a decline of the probability that a child encounters unvaccinated classmates in the kindergarten.
The majority of US states allows non-medical exemptions from mandatory immunization, mostly for religious reasons. “States in the [US] and jurisdictions in other countries should consider adding parental counseling as a requirement for obtaining exemptions to vaccination requirements,” the authors wrote.
1.Omer SB, Allen K, Chang DH, Guterman LB, Bednarczyk RA, Jordan A, Buttenheim A, Jones M, Hannan C, deHart MP, Salmon DA. Exemptions From Mandatory Immunization After Legally Mandated Parental Counseling. Pediatrics 2018; 141(1); doi: 10.1542/peds.2017-2364
Ovarian cancer vaccine promising in early trial
Three of ten patients with advanced ovarian cancers showed partial responses to the cancer vaccine DPX-Survivac (Immunovaccine) in combination with two chemotherapy drugs in a Phase 1b study. The treatment was well tolerated inducing targeted T-cell activation in the majority of participants.
DPX-Survivac contains survivin-derived peptide antigens designed to elicit cytotoxic T-cell responses. Survivin, which is overexpressed in many cancers, antagonizes cell death and promotes angiogenesis in the tumor microenvironment.
The licensure of the first dengue vaccine was suspended in the Philippines over safety concerns
The Philippines has withdrawn the dengue vaccine Dengvaxia (Sanofi) from the market. New data on the vaccine's safety showed that Dengvaxia can exacerbate dengue infections in individuals with no prior exposure to the virus. >700,000 schoolchildren had been immunized before the national campaign was discontinued.
The Philippines’ officials have launched an investigation, while the World Health Organization recommended that only people known to have been infected with dengue should be vaccinated. Dengvaxia, the first licensed dengue vaccine, is used for mass immunization also in Brazil.
Oncolytic virotherapy might boost checkpoint blockade immunotherapy
Infecting brain and breast tumors with an oncolytic virus potentiated immunotherapy in two studies. In the first one, 9 patients with high-grade glioma received intravenous infusion of oncolytic human Orthoreovirus, which penetrated the blood-brain barrier and increased interferon-mediated T-cell response in the tumor microenvironment.1 Moreover, combining virotherapy with PD-1 blockade improved survival in mice.
In the second study, injecting Maraba rhabdovirus into the tumor primed for successful anti-PD-1 treatment in mouse model of triple-negative breast cancer. The combination slowed tumor growth, and when combined with surgical resection, it led to complete response in 60–90% of animals.2
1.Samson A, Scott KJ, Taggart D, West EJ, Wilson E, Nuovo GJ, Thomson S, Corns R, Mathew RK, Fuller MJ, Kottke TJ, Thompson JM, Ilett EJ, Cockle JV, van Hille P, Sivakumar G, Polson ES, Turnbull SJ, Appleton ES, Migneco G, Rose AS, Coffey MC, Beirne DA, Collinson FJ, Ralph C, Alan Anthoney D, Twelves CJ, Furness AJ, Quezada SA, Wurdak H, Errington-Mais F, Pandha H, Harrington KJ, Selby PJ, Vile RG, Griffin SD, Stead LF, Short SC, Melcher AA. Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. Sci Transl Med 2018; 10(422); doi: 10.1126/scitranslmed.aam7577
2.Bourgeois-Daigneault MC, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, Falls T, St-Germain LE, Pelin A, Lichty BD, Stojdl DF, Ungerechts G, Diallo JS, Bell JC. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med 2018; 10(422); doi: 10.1126/scitranslmed.aao1641
Zika vaccine candidate promising in Phase 1 trials
The inactivated Zika vaccine ZPIV elicited robust neutralizing antibody responses in almost all subjects tested in three Phase 1 trials.1 In the randomized, double-blind, placebo-controlled studies, 67 healthy adults received two doses of ZPIV or placebo. More participants are being recruited to test higher doses and a 3-dose regimen.
ZPIV is a purified, formalin-inactivated Zika vaccine derived from the 2015 Puerto Rican strain. It elicited complete protection in preclinical challenge studies.
1.Modjarrad K, Lin L, George SL, Stephenson KE, Eckels KH, De La Barrera RA, Jarman RG, Sondergaard E, Tennant J, Ansel JL, Mills K, Koren M, Robb ML, Barrett J, Thompson J, Kosel AE, Dawson P, Hale A, Tan CS, Walsh SR, Meyer KE, Brien J, Crowell TA, Blazevic A, Mosby K, Larocca RA, Abbink P, Boyd M, Bricault CA, Seaman MS, Basil A, Walsh M, Tonwe V, Hoft DF, Thomas SJ, Barouch DH, Michael NL. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials. Lancet 2017; doi: 10.1016/S0140-6736(17)33106-9
Vaccine and immunotherapy will be tested in patients with HPV-related cancers
The checkpoint inhibitor cemiplimab (Regeneron & Sanofi) in combination with the therapeutic HPV vaccine ISA101 (ISA Pharma) will enter clinical trials involving patients with cervical and head-and-neck cancers. ∼60% of these cancers are caused by HPV16, which is targeted by both drugs.
Cemiplimab is a PD-1-targeting MAb, while ISA101 consists of synthetic long peptides designed to mimic oncogenic antigens.
Phase 3 started for a hepatitis B vaccine candidate
A large-scale two-part study will investigate the effectiveness of the Sci-B-Vac hepatitis B vaccine (VBI Vaccines). The first part, which will enroll 1,600 adults, will compare vaccine immunogenicity to the vaccine currently in broad use, Engerix-B (GSK), in people over 45 years of age in a three-dose regimen. The second part will investigate the vaccine's consistency of immunogenicity in 3,200 adults.
Sci-B-Vac has been licensed in 15 countries and administered to >500,000 people. It targets the hepatitis B virus Large surface protein consisting of S, preS1 and preS2 antigen domains.
Anti-opioid vaccine effective in a preclinical study
An opioid vaccine successfully prevented heroin-induced physiological and behavioral changes in mice and rats.1 The tetanus toxoid-conjugated, liposome-formulated vaccine elicits antibodies that prevent heroin to cross the blood-brain barrier. It could be used to treat substance abuse disorders in the future.
The vaccine did not interfere with substances used to treat addiction or overdose, nor with opioid pain-killers. “Although we are still in the early phase, this study suggests that vaccination can be used together with standard therapies to prevent the withdrawal and craving symptoms associated with opioid withdrawal,” senior author Gary Matyas of Walter Reed Army Institute of Research said.
1.Sulima A, Jalah R, Antoline JFG, Torres OB, Imler GH, Deschamps JR, Beck Z, Alving CR, Jacobson AE, Rice KC, Matyas GR. A Stable Heroin Analogue That Can Serve as a Vaccine Hapten to Induce Antibodies That Block the Effects of Heroin and Its Metabolites in Rodents and That Cross-React Immunologically with Related Drugs of Abuse. J Med Chem 2017; doi: 10.1021/acs.jmedchem.7b01427