T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

Abstract

The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4+ T cell epitopes – without perturbing native antigen structure – by galvanizing HA-specific memory helper T cells that support sustained antibody development against the native target HA. The premise for this vaccine concept rests on (i) the significance of CD4+ T cell memory to influenza immunity, (ii) the essential role CD4+ T cells play in development of neutralizing antibodies, (iii) linked specificity of HA-derived CD4+ T cell epitopes to antibody responses, (iv) the structural plasticity of HA and (v) an illustration of improved antibody response to a prototype engineered recombinant H7-HA vaccine. Immune engineering can be applied to development of vaccines against pandemic concerns, including avian influenza, as well as other difficult targets.

Population-Predicted MHC Class II Epitope Presentation of SARS-CoV-2 Structural Proteins Correlates to the Case Fatality Rates of COVID-19 in Different Countries

“…Doubtless, many other factors may also contribute to country-specific differences: for instance in some Asian countries such as in Japan may be connected to cultural habits such as many people wearing a face mask even before the pandemic. Nevertheless, for viral diseases such as H7N9 influenza A virus, analysis of T-cell immunity in human populations applying refined immune-informatics provided also here valuable insights such as clear ethnic differences [ 24 , 25 ] and a basis for suitable vaccine strategies including even pandemic preparedness [ 26 ].…”

In silicoidentification and modification of T cell epitopes in pertussis antigens associated with tolerance

“…36 Additional influenza-related immune-engineering studies are ongoing. 44 Several aspects of this study are important for designing the next generation of Bp vaccines. First, lessons were learnt from broadly studied differences between the efficacy of wPV and aPV and between vaccines and natural infections.…”

Immune-engineered H7N9 influenza hemagglutinin improves protection against viral influenza virus challenge

“…This epitope had high similarity with conserved CD4+ stimulating epitope, H3 HA 322-345 . 7 This led to the identification of a highly conserved, HLA-binding 9-mer, predicted to be significantly more immunogenic than its H7 homolog that resulted in the replacement of three amino acids of H7 HA 316-324 peptide 25 and the new HA vaccine candidate was designed H7 OPT1 HA. 8 …”

“…In order to enhance H7 HA vaccines, T cell epitopes were added to the HA antigen to trigger a rapid recall response from preexisting seasonal influenza-specific memory T cells. 7 Approximately ~67% (6 of 9 residues) of the amino acids in the T reg epitopes aligned between the H7 and H3 HA antigens. However, this highly conserved epitope in seasonal H3N2 viruses activates effector, rather than regulatory T cells.…”