Influenza-A H3N2 antibodies are immunoglobulin molecules that recognize conserved or variable epitopes on HA and NA proteins. Their primary roles include:
Neutralization: Blocking HA-mediated viral entry into host cells .
Inhibition of Viral Release: Preventing NA-mediated cleavage of sialic acids to halt viral progeny release .
Cross-Reactivity: Targeting conserved regions (e.g., HA stalk) to provide heterosubtypic protection against diverse H3N2 strains .
Seasonal inactivated influenza vaccines (IIV) induce H3N2-specific monoclonal antibodies (MAbs) that persist in bone marrow plasma cells, enabling long-term protection .
Enhanced vaccines (e.g., MF59-adjuvanted or high-dose) improve antibody responses in older adults, but repeated vaccination with standard-dose formulations reduces immunogenicity due to antigenic imprinting .
Infection triggers polyclonal antibodies against conserved HA stalk regions, which inhibit viral replication in vitro and protect against heterologous strains .
Antibody dynamics exhibit long-term periodicity (4–8 years) due to cross-reactive immune responses to antigenically similar historical strains .
HA glycosylation (e.g., T160 in clade 3C.2a) reduces antibody binding to egg-adapted vaccine strains, lowering vaccine efficacy .
Machine learning models predict H3N2 antigenic drift using HA1 sequence data, achieving a mean absolute error of 0.702 antigenic units per season .
A 2017–2018 Hong Kong study compared antibody responses in older adults receiving different vaccines :
Vaccine Type | GMT Rise (Fold) | Prior Vaccination Impact |
---|---|---|
Standard-dose quadrivalent | 4.2 | 32% reduction |
MF59-adjuvanted trivalent | 6.1 | 25% reduction |
High-dose trivalent | 7.8 | 28% reduction |
Enhanced vaccines partially mitigated the blunted responses observed in repeatedly vaccinated individuals.
Antigenic Mismatch: Egg-adapted vaccine strains often lack critical glycosylation sites present in circulating viruses, necessitating non-egg production systems .
Universal Vaccine Development: Broadly reactive HA stalk and NA "dark side" antibodies are promising targets .
Predictive Modeling: Machine learning integrates genetic and antigenic data to forecast seasonal strain evolution, improving vaccine strain selection .
The H3N2 subtype of Influenza A virus is a significant cause of respiratory infections in humans. The virus is characterized by its surface proteins, hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin is particularly important as it facilitates the virus’s entry into host cells. The HA protein is further divided into two subunits, HA1 and HA2, with HA1 being the primary target for neutralizing antibodies.
Hemagglutinin is a single-pass type I integral membrane glycoprotein that constitutes over 80% of the envelope proteins in the influenza virus particle. It is a trimer with a receptor-binding pocket on the globular head of each monomer. During natural infection, the inactive HA is cleaved into HA1 and HA2 by trypsin-like, arginine-specific endoproteases secreted by bronchial epithelial cells .
The H3N2 subtype of Influenza A virus has undergone significant genetic drift, resulting in various strains. The HA1 subunit of H3N2 is particularly prone to mutations, which can lead to antigenic drift and the emergence of new strains. This makes it challenging to develop long-lasting vaccines and necessitates the continuous monitoring and updating of vaccine strains .
Mouse anti-human antibodies are monoclonal antibodies derived from mice that are immunized with human antigens. In the context of H3N2/HA1, these antibodies are generated by immunizing mice with recombinant human H3N2/HA1 proteins. The spleen cells from these immunized mice are then fused with myeloma cells to create hybridoma cells that produce the desired monoclonal antibodies .
Mouse anti-human H3N2/HA1 antibodies are widely used in research and diagnostic applications. They are crucial for developing ELISA kits, which are used to quantitatively determine the presence of H3N2/HA1 in various samples, including plasma and tissue homogenates . These antibodies are also used in studying the immune response to influenza infections and in the development of new vaccines .