Safety and Immunogenicity of a Plant-Produced Recombinant Hemagglutinin-Based Influenza Vaccine (HAI-05) Derived from A/Indonesia/05/2005 (H5N1) Influenza Virus: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study in Healthy Adults

Abstract

Recently, we have reported [1,2] on a subunit influenza vaccine candidate based on the recombinant hemagglutinin protein from the A/Indonesia/05/2005 (H5N1) strain of influenza virus, produced it using ‘launch vector’-based transient expression technology in Nicotiana benthamiana, and demonstrated its immunogenicity in pre-clinical studies. Here, we present the results of a first-in-human, Phase 1 randomized, double-blind, placebo-controlled study designed to investigate safety, reactogenicity and immunogenicity of three escalating dose levels of this vaccine, HAI-05, (15, 45 and 90 µg) adjuvanted with Alhydrogel® (0.75 mg aluminum per dose) and the 90 µg dose level without Alhydrogel®. Vaccine was administered intramuscularly in two injections three weeks apart to healthy adults of 18–49 years of age. At all dose levels the vaccine was generally safe and well tolerated, with no reported serious adverse events or dose-limiting toxicities. Mild local and systemic reactions were observed in all vaccine dose groups and the placebo group and their occurrence was not dose related. The incidence rates were higher in the groups receiving vaccine with Alhydrogel®. The immune response elicited by the HAI-05 vaccine was variable with respect to both hemagglutination-inhibition and virus microneutralization antibody titers, with the highest responses observed in the 90 µg unadjuvanted group.

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

“…Manufacturing processes based on transient expression of proteins in plants and similar to those described in this report have already been brought into FDA Good Manufacturing Practice (GMP) compliance, and several biopharmaceuticals produced transiently in plants are currently undergoing clinical studies (26)(27)(28).…”

Current Issues with Influenza Management

“…Again, as adamantanes are not recommended, they were not considered in the most recent guidance. While cost-effectiveness of the NA inhibitors varied with the population assessed (healthy adult, 'at-risk' adult, healthy children, 'at risk' children, and elderly), overall both oseltamivir and zanamivir were shown to have cost benefits, reducing costs associated with symptoms, complications and hospitalizations [83]. However, a more recent study assessing the cost-effectiveness of antiviral drug use and other interventions during a pandemic highlights the distinct outcomes depending on the severity of pandemic, where a low-severity pandemic (similar to 2009) showed no cost benefit of antiviral drug use [84].…”

“…In a systematic review of prevention and treatment of influenza virus infection published in 2003, Turner et al assigned average costs for treatment or prophylaxis with amantadine, oseltamivir and zanamivir [82]. These costs have subsequently been used in guidelines released by the UK and the USA [83], but may not reflect real costs at the pharmacy. While amantadine is notably less expensive than the NA inhibitors (Table 6.3), the adamantanes are not recommended for treatment or prophylaxis due to widespread resistance among circulating influenza viruses [1,3].…”

Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

“…Most formulations require high doses, repeat immunization, or adjuvant formulation for effective and protective immune activation in animal models 18,21 and in clinical trials. 22,23 Our work has focused on developing an alternative plant-produced HA subunit vaccine with improved immunogenicity that can provide single-dose protection against virus challenge. Rapid Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge Jyothi Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production.…”