Focused antibody response to influenza linked to antigenic drift

Chang

et al. 2017

Sci Rep

Self Cite

Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005–2008. Serological antibody responses were measured by hemagglutination-inhibition (HI) test. Subjects with repeated vaccination had higher pre-vaccination and lower post-vaccination HI titer than those with first vaccination, although serological responses between groups might vary with different antigen types and while the drifted strain was introduced in the vaccine. Higher fold rise in the HI titer was observed in the group with first than repeated vaccination and the fold increase in the HI titer was inversely correlated with pre-vaccination titer in 2007 and 2008. Nevertheless, no significant difference in the day 28 seroprotection rate was observed between groups with repeated and first vaccination in most circumstances. Further studies are needed to understand the long-term effect of repeated vaccination on the antibody response both at the serological and repertoire levels among health care personnel.

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Antibody Responses to Trivalent Inactivated Influenza Vaccine in Health Care Personnel Previously Vaccinated and Vaccinated for The First Time

Chang

et al. 2017

Sci Rep

Self Cite

“…One set of antibodies was isolated from human volunteers primed with chimpanzee adenovirus expressing Zaire GP (ChAD3 EBO Z) and boosted with MVA-BN Filo (modified Vaccinia expressing Ebola, Sudan and Marburg virus GPs and Taï Forest virus NP) vaccines (Ewer et al, 2016). Antibodies were purified as described in Huang et al (Huang et al, 2015). Another mAb set was derived using recombinant EBOVGPΔmucin (GenBank: KM233090) or two rounds of panning with EBOVGPΔmucin followed by two rounds of panning with rEBOVGP33-308 (GenBank: AAC54887.1) or EBOVGPΔmucin followed by one round of panning with rEBOVGP33-308.…”

Section: Star Methodsmentioning

confidence: 99%

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection

Saphire

Schendel

Fusco

et al. 2018

Cell

Self Cite

176

240

SUMMARY Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.

Current Opinion in Virology

“…An example of this was seen following the 2009 H1N1 pandemic. Most individuals infected with the 2009 pandemic H1N1 virus mounted antibody responses against epitopes that were conserved in older seasonal H1N1 viruses [20,23,34,35]. Following exposure with the 2009 H1N1 virus, humans produced antibodies of different specificities depending on the specific seasonal H1N1 virus that they were exposed to in childhood [20,35,36].…”

Section: A Contemporary Synthesismentioning

confidence: 99%

Immune history and influenza virus susceptibility

Cobey

Hensley

2017

210

222

Antibody responses to influenza viruses are critical for protection, but the ways in which repeated viral exposures shape antibody evolution and effectiveness over time remain controversial. Early observations demonstrated that the history of viral exposures has a profound effect on the specificity and magnitude of antibody responses to a new viral strain, a phenomenon called “original antigenic sin.” Although “sin” might suppress some aspects of the immune response, so far there is little indication that hosts with pre-existing immunity are more susceptible to viral infections compared to naïve hosts. However, the tendency of the immune response to focus on previously recognized conserved epitopes when encountering new viral strains can create an opportunity cost when mutations arise in these conserved epitopes. Hosts with different exposure histories may continue to experience distinct patterns of infection over time, which may influence influenza viruses’ continued antigenic evolution. Understanding the dynamics of B cell competition that underlie the development of antibody responses might help explain the low effectiveness of current influenza vaccines and lead to better vaccination strategies.