TY - JOUR
T1 - Re-engaging cross-reactive memory B cells
T2 - The influenza puzzle
AU - Ellebedy, Ali H.
AU - Ahmed, Rafi
PY - 2012
Y1 - 2012
N2 - The emergence of a novel influenza A virus strain into humans poses a continuous public health threat. Vaccination is the most effective means of protection against influenza. The generation of memory B cells and long-lived plasma cells that can maintain protective levels of influenza-specific antibodies for protracted periods of time is the foundation for the success of such vaccines. Influenza vaccines elicit an antibody response that is primarily targeting viral surface glycoproteins. However, frequent amino acid mutations within the immunodominant epitopes allow the virus to efficiently escape neutralization by preexisting antibodies and consequently cause annual epidemics and occasional pandemics. Recently, monoclonal antibodies (mAbs) that target subdominant influenza epitopes have been extensively characterized. These epitopes are immunogenic, can mediate virus neutralization, and most importantly are conserved among different influenza strains. It remains puzzling, however, that despite being repeatedly exposed to such conserved domains of influenza hemagglutinin (HA) either in the form of vaccination or natural infection, most humans do not develop immunological memory that can provide broad protection against emerging virus strains. Here we will discuss the conditions that may be required for engaging such cross-reactive memory B cells in the immune response to influenza infection and vaccination in humans.
AB - The emergence of a novel influenza A virus strain into humans poses a continuous public health threat. Vaccination is the most effective means of protection against influenza. The generation of memory B cells and long-lived plasma cells that can maintain protective levels of influenza-specific antibodies for protracted periods of time is the foundation for the success of such vaccines. Influenza vaccines elicit an antibody response that is primarily targeting viral surface glycoproteins. However, frequent amino acid mutations within the immunodominant epitopes allow the virus to efficiently escape neutralization by preexisting antibodies and consequently cause annual epidemics and occasional pandemics. Recently, monoclonal antibodies (mAbs) that target subdominant influenza epitopes have been extensively characterized. These epitopes are immunogenic, can mediate virus neutralization, and most importantly are conserved among different influenza strains. It remains puzzling, however, that despite being repeatedly exposed to such conserved domains of influenza hemagglutinin (HA) either in the form of vaccination or natural infection, most humans do not develop immunological memory that can provide broad protection against emerging virus strains. Here we will discuss the conditions that may be required for engaging such cross-reactive memory B cells in the immune response to influenza infection and vaccination in humans.
KW - B cells
KW - Cross-reactive
KW - Epitopes
KW - Influenza
KW - Memory
UR - http://www.scopus.com/inward/record.url?scp=84874187612&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2012.00053
DO - 10.3389/fimmu.2012.00053
M3 - Review article
C2 - 22566934
AN - SCOPUS:84874187612
SN - 1664-3224
VL - 3
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - MAR
M1 - Article 53
ER -