Abstract
H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.
Highlights
The H5 highly pathogenic avian influenza viruses from the genetic clade 2.3.4.4 emerged in China in 2010–2011
Computationally Optimized Broadly Reactive Antigens (COBRA) H5 HA vaccines were designed using H5Nx HA sequences downloaded from GISIAD (Supplemental Table S1)
As part of universal vaccine development, next-generation influenza virus vaccines should protect against seasonal IAV and IBV antigenic drift, and against the emergence of novel strains and subtypes not currently circulating in the human population
Summary
The H5 highly pathogenic avian influenza viruses from the genetic clade 2.3.4.4 emerged in China in 2010–2011. These viruses were detected in birds in more than 24 countries in the eastern hemisphere [1]. As of February 2020, the World Health Organization (WHO) reported 24 cases of human infections [2] by viruses of the H5N6 subtype, which is the only 2.3.4.4 clade H5 influenza virus that has infected people [3]. In 2014, H5N8 Eurasian subtypes was detected in U.S Washington state in captive falcons, wild birds, and poultry [5,6] These viruses spread across the central regions of North America devastating the poultry industry [6].
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