A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1

Abstract

BackgroundThe highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission.Methodology/Principal FindingsIn the present study we evaluated the vaccine potential of recombinant soluble trimeric subtype 5 hemagglutinin (sH53) produced in mammalian cells. The secreted, purified sH53 was biologically active as demonstrated by its binding to ligands in a sialic acid-dependent manner. It was shown to protect chickens, in a dose-dependent manner, against a lethal challenge with H5N1 after a single vaccination. Protected animals did not shed challenge virus as determined by a quantitative RT-PCR on RNA isolated from trachea and cloaca swabs. Also in mice, vaccination with sH53 provided complete protection against challenge with HPAI H5N1.Conclusions/SignificanceOur results demonstrate that sH53 constitutes an attractive vaccine antigen for protection of chickens and mammals against HPAI H5N1. As these recombinant soluble hemagglutinin preparations can be produced with high yields and with relatively short lead time, they enable a rapid response to circulating and potentially pandemic influenza viruses.

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

“…Together, these data indicate that nonadjuvanted sH5 3 antigen is able to elicit high titers of H5 cross-clade neutralizing antibody when administered using a prime/boost/boost regimen. Consistent with previous reports, 6,7,12 multiple immunizations of sH5 3 recombinant protein were required to generate consistently high neutralizing antibody titers.…”

“…4 Recent studies demonstrated that rHA engineered to form a stable trimeric configuration elicited a protective immune response in vaccinated animals. [5][6][7][8][9][10] Neutralizing antibody levels and protection from disease were enhanced in mice vaccinated with soluble rHA trimers as compared to animals vaccinated with rHA monomers, 5,8 indicating the importance of immunogens that mimic those expressed by the infectious agent. Along these lines, the composition and/or number of N-linked glycans on rHA trimers have been shown to modify the level of the protective antibody response.…”

“…6,7,12 Polyanhydride nanoparticles have been shown to be a versatile vaccine adjuvant/delivery platform capable of enhancing the immune response to recombinant proteins. [13][14][15] Polyanhydrides are biodegradable materials that provide sustained release kinetics of encapsulated antigens, resulting in long-lived, high-avidity antibody titers, even with suboptimal doses of antigen.…”

“…By day 42, the majority of mice in both immunization groups had detectable neutralizing antibody titers (ie, .50) that were greater than protective titers reported in the literature. 7,8 However, the response was highly variable among individual mice, with ID 50 titers ranging from undetectable to greater than 1,000. Neutralization titers significantly increased following a second boost (day 63), with mean neutralization antibody titers of greater than 10,000.…”

A lack of antibody formation against inactivated influenza virus after aerosol vaccination in presence or absence of adjuvantia

“…Stimune, also known as Specol, has been used successfully in an i.m. vaccine using soluble trimeric H5 protein in chicken (Cornelissen et al, 2010).…”