Article ; Online: An Improved Inactivated Influenza Vaccine with Enhanced Cross Protection.
2018 Volume 9, Page(s) 1815
Abstract: Current inactivated influenza vaccines are strain-specific and poorly effective against variant or mismatched viruses. They are standardized based on their hemagglutinin (HA) or ability to induce strain-specific hemagglutination inhibition (HAI) ... ...
| Abstract | Current inactivated influenza vaccines are strain-specific and poorly effective against variant or mismatched viruses. They are standardized based on their hemagglutinin (HA) or ability to induce strain-specific hemagglutination inhibition (HAI) antibodies. The HA is known to undergo major conformational changes when exposed to the low pH environment of endosomes (pH 5.0 and 37°C), which are required for membrane fusion during virus cell entry. In an effort to improve these vaccines, influenza antigens treated under various low pH conditions were evaluated for increased cross-reactive antibody response and cross protection. It was found that a full range of structural and antigenic changes in HA could be induced by varying low pH treatment conditions from the mild (low pH at ≤25°C) to the strong (low pH at ≥37°C) as determined by analysis of potency, HA morphology, protease sensitivity, and reactivity with an anti-HA2 domain (CD) antibody. Inactivated antigens of both H1N1 and H3N2 strains treated at mild low pH conditions (0-25°C) exhibited only moderate HA structural and antigenic changes and markedly increased antibody response against HA2, the highly conserved part of HA, and cross protection against heterologous challenge in mice by up to 30% in survival. By contrast, antigen treated with low pH at 37°C showed more extensive structural and antigenic changes, and induced much less of an increase in antibody response against HA2, but a greater increase with response against HA1, and did not provide any increased cross protection. These results suggest that the increased response against HA2 obtained with the mild low pH treatment is associated with the increased cross protection. These antigens treated at the mild low pH conditions remained capable of inducing a high level of strain-specific HAI antibodies. Thus, they could readily be formulated as an inactivated influenza vaccine which not only provides the same strain-specific protection but also an increased cross protection against heterologous viruses. Such a vaccine could be particularly beneficial in cases of vaccine mismatch. |
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| MeSH term(s) | Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Cross Protection/immunology ; Cross Reactions ; Enzyme-Linked Immunosorbent Assay ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Hydrogen-Ion Concentration ; Immunization ; Immunogenicity, Vaccine ; Influenza A virus/classification ; Influenza A virus/immunology ; Influenza A virus/ultrastructure ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Mice ; Neutralization Tests ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/prevention & control ; Vaccines, Inactivated/administration & dosage ; Vaccines, Inactivated/immunology |
| Chemical Substances | Antibodies, Neutralizing ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines ; Vaccines, Inactivated |
| Language | English |
| Publishing date | 2018-08-09 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2018.01815 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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