Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets

Abstract

Background and MethodsHighly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets.ResultsThe serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus.ConclusionOur findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate.Trial RegistrationClinicalTrials.gov NCT00868218

Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model

“…The trial was performed in early 2009 at the Haukeland University Hospital in Bergen, Norway, with samples being collected prevaccination (day 0), postvaccination after one dose (day 21), and postvaccination after the second dose (day 42). Additional information for the clinical trial can be found on ClinicalTrials.gov website (NCT00868218) identifier ( 20 , 21 , 38 ).…”

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…A number of novel adjuvants, such as microcrystalline tyrosine, Matrix M, pathogen-associated molecular patterns, and chitosan, are in development. [111][112][113][114] DNA and RNA vaccines induce an immune response to the nucleic acid-encoded antigen. 115 Impressive results have been reported in animals for a single low-dose intradermal, nonreplicating DNA vaccine for RSV; however, whether this will translate effectively to human subjects is not yet known.…”

Enabling Vaccine Delivery Platforms and Adjuvants for Malaria

“…High levels of in vitro erythrocyte binding inhibition (>90%) were achieved with Matrix-M formulations in this study [94]. Additionally, Matrix-M has been assessed in a Phase I clinical study in combination with chimpanzee adenovirus 63 [95]. Similar to Matrix-M, ISCOMs have a mean diameter of ~40 nm; however, this technology incorporates antigens into the ISCOM such that they are displayed in a multimeric fashion on the particles.…”