Zika vaccine development reaches clinical trials
There are a number of Zika vaccine and antibody candidates in development. The latest to enter clinical trials is a DNA vaccine candidate developed by the U.S. National Institutes of Health (NIH). It is based on the same technology that NIH used for a West Nile virus vaccine, and it will be evaluated for safety and immunogenicity in 80 adults aged 18-35 years.
Another DNA vaccine candidate and a purified inactivated virus vaccine conferred robust protection in rhesus monkeys, as did Zika-specific neutralizing antibodies transferred to naïve subjects.1
In addition, several studies suggest that dengue-specific antibodies can neutralize Zika. Both viruses are members of the Flaviviridae family, and they share a common epitope–a site of interaction of the envelope protein dimer with the precursor membrane protein–which is targeted by some antibodies isolated from dengue-infected patients.2 However, another study has shown that the serological cross-reaction can lead to antibody-mediated enhancement of Zika infection, which leaves the significance of this observation in question.3
1.Abbink P, Larocca RA, De La Barrera RA, Bricault CA, Moseley ET, Boyd M, Kirilova M, Li Z, Ng'ang'a D, Nanayakkara O, Nityanandam R, Mercado NB, Borducchi EN, Agarwal A, Brinkman AL, Cabral C, Chandrashekar A, Giglio PB, Jetton D, Jimenez J, Lee BC, Mojta S, Molloy K, Shetty M, Neubauer GH, Stephenson KE, Peron JP, Zanotto PM, Misamore J, Finneyfrock B, Lewis MG, Alter G, Modjarrad K, Jarman RG, Eckels KH, Michael NL, Thomas SJ, Barouch DH. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science 2016; doi: 10.1126/science.aah6157
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; 536(7614):48-53.
3.Dejnirattisai W, Supasa P,, Wongwiwat W, Rouvinski A, Barba-Spaeth G, Duangchinda T, Sakuntabhai A, Cao-Lormeau VM, Malasit P, Rey FA, Mongkolsapaya J, Screaton GR. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with Zika virus. Nat Immunol 2016; 17(9):1102-8
FluMist live attenuated influenza vaccine was found as efficacious as inactivated vaccine
The trivalent live attenuated influenza vaccine (LAIV) FluMist (AstraZeneca) protects subjects from virus infection equally well as the more common trivalent inactivated influenza vaccine (IIV). A study published in Annals of Internal Medicine1 monitored >1,000 Canadian children aged 3-15 years from Hutterite communities over three seasons, and found that infection occurred at rates of 5.3% and 5.2% in the LAIV and IIV groups, respectively. At the same time, the U.S. Centers for Disease Control and Prevention (CDC) committee has advised against the use of the newer quadrivalent FluMist based on data that suggest only 3% efficacy.
1.Loeb M, Russell ML, Manning V, Fonseca K, Earn DJ, Horsman G, Chokani K, Vooght M, Babiuk L, Schwartz L, Neupane B, Singh P, Walter SD, Pullenayegum E. Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial. Ann Intern Med 2016; doi: 10.7326/M16-0513
Customizable RNA vaccines protected mice against various challenges
An easy-to-make RNA vaccine delivery system was successfully used to immunize mice against Ebola, H1N1 influenza and Toxoplasma gondii. According to a study published in PNAS,1 the RNA, which can encode proteins from various pathogens, is encapsulated in branched dendrimer nanoparticles. The vaccines were used in single dose, adjuvant-free formulation, and all had 100% efficacy in a mouse challenge model.
The platform enables vaccine production in one week, noted lead author Jasdave Chahal of Whitehead Institute for Biomedical Research. “Typically a vaccine becomes available long after the outbreak is over. We think we can become interventional over the course of a real outbreak.” The researchers plan to use the platform for the development of cancer vaccines.
1.Chahal JS, Khan OF, Cooper CL, McPartlan JS, Tsosie JK, Tilley LD, Sidik SM, Lourido S, Langer R, Bavari S, Ploegh HL, Anderson DG. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A 2016; 113(29):E4133-42
Another universal influenza vaccine candidate enters clinical trials
A universal influenza vaccine RedeeFlu (FluGen) is tested for safety and immunogenicity in a randomized, placebo-controlled, dose-ranging Phase 1 trial involving 96 healthy adults aged 18-49. RedeeFlu is H3N2 strain deleted in M2 gene, which prevents it from mounting infection, but allows expression of full repertoire of influenza antigens.
The vaccine elicited robust antibody and T-cell responses in preclinical studies, and demonstrated protection against both drifted and mismatched strains of influenza.
Early immunotherapy promising in treating peanut allergy
Oral immunotherapy in allergic pre-schoolers allowed >3/4 of them to re-introduce peanut into their diets. In a study conducted by the U.S. NIH,1 40 children aged 9-36 months with suspected or known allergy were given low or high doses of peanut-containing immunotherapy in the course of a median period of 29 months. Four weeks after the last dose, these subjects were 19 times more likely to successfully consume dietary peanut than a control group of 150 untreated children. The oral immunotherapy was safe with only mild side-effects such as abdominal pain, and the peanut-specific IgEs were markedly reduced in both experimental cohorts compared to controls.
1.Vickery BP, Berglund JP, Burk CM, Fine JP, Kim EH, Kim JI, Keet CA, Kulis M, Orgel KG, Guo R, Steele PH, Virkud YV, Ye P, Wright BL, Wood RA, Burks AW. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol 2016; doi: 10.1016/j.jaci.2016.05.027
Norovirus vaccine candidate is tested in a Phase 1 trial
A recombinant VP1 protein-based norovirus vaccine (Vaxart) has entered clinical trials in a randomized, double-blind, placebo-controlled study involving 66 healthy adults. Safety and immunogenicity of the thermostable tablet vaccine will be monitored for a year.
There is no approved vaccine against norovirus, which affects ∼20 million people in the U.S. alone, and results in >500 deaths.
Nivolumab failed Phase 3 trial in NSCLC as a first-line monotherapy
The anti-PD1 MAb nivolumab (Opdivo, BMS) did not succeed in a monotherapy setting in patients with previously untreated non-small-cell lung cancer (NSCLC). The Phase 3 CheckMate-026 study compared nivolumab to chemotherapy in >500 patients with both squamous and non-squamous tumors.
The MAb, which blocks a T-cell-suppression pathway that cancers use to evade the immune response, was previously approved as a second-line treatment in patients who failed prior chemotherapy. It is also being investigated in combination with other immunotherapeutics.
U.S. parents are not keen on mandating HPV vaccination; vaccine refusals grow
Only one in five U.S. parents support school-entry requirement for children to be vaccinated against HPV. According to a nationwide study that asked 1,500 parents of 11- to 17-year-olds,1 support rose to 57% if the law would include opt-out provisions. Thus far, only Virginia, Rhoda Island and Washington, D.C. require HPV vaccination for school entry, and the HPV vaccination is received by only 40% of girls and 21% of boys, according to the CDC.
In addition, a pair of surveys among U.S. pediatricians suggested that the number of parents that refuse to give their child a vaccine rose between 2006 and 2013.2 Not only did the proportion of doctors that had encountered a refusal increase from 75% to 87%, but the pediatricians also estimated that the percentage of refusing parents increased almost two-fold. Many of the parents believed immunization was unnecessary.
1.Calo WA, Gilkey MB, Shah PD, Moss JL, Brewer NT. Parents' Support for School-Entry Requirements for Human Papillomavirus Vaccination: A National Study. Cancer Epidemiol Biomarkers Prev 2016; 25(9):1317-25
2.Hough-Telford C, Kimberlin DW, Aban I, Hitchcock WP, Almquist J, Kratz R, O'Connor KG. Vaccine Delays, Refusals, and Patient Dismissals: A Survey of Pediatricians. Pediatrics 2016; doi: 10.1542/peds.2016-2127
Ebola vaccine candidate has been prioritized in both the U.S. and EU
The Ebola vaccine rVSV-ZEBOV (Merck) has received Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA), as well as Priority Medicines status by the European Medicines Agency. The vaccine's development will thus be expedited, and the manufacturer will seek approval in 2017. rVSV-ZEBOV is a live attenuated recombinant vesicular stomatitis virus that expresses Zaire Ebola surface glycoproteins.
A new quadrivalent influenza vaccine approved in the U.S.
The FDA has approved Afluria Quadrivalent (Seqirus) seasonal influenza vaccine for adults. The decision was based on a randomized, double-blind Phase 3 clinical trial, in which Afluria demonstrated non-inferior immunogenicity compared to two trivalent vaccines in 3,500 adult subjects. Afluria is an inactivated vaccine containing two type-A and two type-B strains of influenza.