Antibodies induced by the HA2 glycopolypeptide of influenza virus haemagglutinin improve recovery from influenza A virus infection

Abstract

The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus haemagglutination, neutralize virus infectivity and provide good protection against infection, but do not cross-react with the HA of other subtypes. Little is known regarding the biological activities of antibodies against HA2. To study the role of antibodies directed against HA2 during influenza virus infection, two vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA, in which HA1 and HA2 were derived from different HA subtypes. The KG-11 recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2) virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA subtype homologous to the challenge virus [A/PR/8/34 (H1N1) or A/Mississippi/1/85 (H3N2)] did not prevent virus infection, but nevertheless resulted in an increase in mice survival and faster elimination of virus from the lungs. Passive immunization with antibodies purified from mice immunized with rVVs confirmed that antibodies against HA2 were responsible for the described effect on virus infection. Based on the facts that HA2 is a rather conserved part of the HA and that antibodies against HA2, as shown here, may moderate virus infection, future vaccine design should deal with the problem of how to increase the HA2 antibody response.

Two distinct regions of HA2 glycopolypeptide of influenza virus hemagglutinin elicit cross-protective immunity against influenza

“…These results are in accordance with previous data on protective immunity induced by immunization with hA2, which was expressed by recombinant vaccinia viruses (Gocník et al, 2008) or E. coli (Bommakanti et al, 2010). In this work, we purified ehA2 according to chen et al (1995).…”

“…Moreover, there are some regions of hA2 gp, which are conserved also among various subtypes (varečková et al, 2002, 2008). As we have shown previously, hA2 gp is immunogenic and able to induce a protective antibody response in mice (varečková et al, 2003a;Gocník et al, 2008). The most conserved part of hA2 gp is its n-terminus, FP.…”

“…Many studies have been focused on the M2 protein (okuda et al, 2001;Fan et al, 2004;liu et al, 2004;DeFilette et al, 2006;hoelscher et al, 2006;DeFilette et al, 2008a,b;huleatt et al, 2008;Zhang et al, 2009;li et al, 2011;Park et al, 2011;Staneková et al, 2011), but recently also the conserved part of hA, hA2 gp, was used as an inductor of cross-protective immunity (okuno et al, 1993;horváth et al, 1998;Gocník et al, 2008;Sui et al, 2009;Bommakanti et al, 2010;Steel et al, 2010;Wang et al, 2010;Staneková et al, 2011). The latter was the subject of our interest for several years.…”

Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection

“…Previous studies have suggested that HA2 could contain a potential epitope responsible for the induction of antibodymediated protective immunity (9). In the present study, a panel of MAbs against HA2 gp was characterized for their respective epitopes by epitope mapping.…”

Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses

“…HA2 gp is a relatively conserved protein, and some HA2 epitopes are even shared among HA subtypes (Kostolanský et al, 2002;Varečková et al, 2008). HA2-specific antibodies recognizing HA stem were shown to be protective (Gocník et al, 2007(Gocník et al, , 2008Prabhu et al, 2009;Sui et al, 2009;Wang et al, 2010;Staneková et al, 2011;Janulíková et al, 2012), though they do not mediate virus neutralization by blocking the receptor-binding site on HA. We therefore suggest that anti-stem HA antibodies could help individuals exposed to dangerous avian IAV to overcome the infection in a subclinical manner.…”