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1.
Front Immunol ; 9: 2350, 2018.
Article in English | MEDLINE | ID: mdl-30369928

ABSTRACT

Seasonal influenza vaccines are updated almost annually to match the antigenic drift in influenza hemagglutinin (HA) surface glycoprotein. A new HA stem-based antigen, the so-called "mini-HA," was recently shown to induce cross-protective antibodies. However, cross-reactive antibodies targeting the HA stem can also be found in mice and humans after administration of seasonal vaccine. This has raised the question whether in similar conditions such a mini-HA would be able to show an increased breadth of protection over immunization with full length (FL) HA. We show in mice that in a direct comparison to H1 FL HA, using the same immunization regimen, dosing and adjuvant, a group 1 mini-HA has a higher protective efficacy against group 1 influenza virus challenges not homologous to the H1 FL HA. Although both antigens induce a similar breadth of HA subtype binding, mini-HA immunization induces significantly more HA stem-specific antibodies correlating with survival. In addition, both mini-HA and H1 FL HA immunization induce influenza neutralizing antibodies while mini-HA induces significantly higher levels of mFcγRIII activation, involved in Fc-mediated antibody effector functions. In agreement with previous findings, this confirms that more than one mechanism contributes to protection against influenza. Together our results further warrant the development of a universal influenza vaccine based on the HA stem region.


Subject(s)
Antibodies, Viral/immunology , Antibody Specificity/immunology , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunization , Influenza Vaccines/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Animals , Antibodies, Neutralizing/immunology , Antibody-Dependent Cell Cytotoxicity , Antigens, Viral/immunology , Cross Reactions/immunology , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Immunity, Cellular , Immunoglobulin G/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Mice , Neutralization Tests , Orthomyxoviridae Infections/mortality , Protein Binding/immunology
2.
NPJ Vaccines ; 3: 25, 2018.
Article in English | MEDLINE | ID: mdl-29977611

ABSTRACT

Seasonal vaccines are currently the most effective countermeasure against influenza. However, seasonal vaccines are only effective against strains closely related to the influenza strains contained in the vaccine. Recently a new hemagglutinin (HA) stem-based antigen, the so-called "mini-HA", has been shown to induce a cross-protective immune response in influenza-naive mice and non-human primates (NHP). However, prior exposure to influenza can have a profound effect on the immune response to subsequent influenza infection and the protective efficacy of vaccination. Here we show that mini-HA, compared to a trivalent influenza vaccine (TIV), elicits a broadened influenza-specific humoral immune response in NHP previously exposed to influenza. Serum transfer experiments showed that antibodies induced by both mini-HA and seasonal vaccine protected mice against lethal challenge with a H1N1 influenza strain heterologous to the H1 HA included in the TIV. However, antibodies elicited by mini-HA showed an additional benefit of protecting mice against lethal heterosubtypic H5N1 influenza challenge, associated with H5 HA-specific functional antibodies.

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