Refocusing the Immune Response to Selected Epitopes on a Zika Virus Protein Antigen by Nanopatterning

Abstract

Infections with Zika virus (ZIKV) are linked to the development of severe central nervous system disorders, but the need for a ZIKV vaccine remains unmet. Although the design of vaccines that elicit antibodies targeting domain III (DIII) of the ZIKV envelope (E) protein as an antigen is an attractive strategy, poorly neutralizing or cross‐reactive antibodies that target the E protein may lead to antibody‐dependent enhancement of disease. It is therefore decided to use the previously reported nanopatterning technique, which combines the site‐specific incorporation of non‐canonical amino acids with site‐specific functionalization of the protein with polyethylene glycol (PEG), to shield selected epitopes on DIII. Two different nanopatterned DIII variants are designed and characterized and demonstrate that epitope shielding with PEG completely inhibits the binding of epitope‐specific antibodies in vitro. Furthermore, immunization with multivalent nanopatterned DIII antigens results in the refocusing of the antibody response toward the exposed epitopes on the protein surface and away from potentially enhancing epitopes. This ability to redirect the antibody response toward targeted regions of the DIII protein should be useful for the design of effective and safe ZIKV vaccines.

Nanovaccines Displaying the Influenza Virus Hemagglutinin in an Inverted Orientation Elicit an Enhanced Stalk‐Directed Antibody Response

“…To develop a virion-like scaffold that could be used to present the HA in varying orientations (Figure 1), we generated streptavidincoated VLPs that can display biotinylated protein by exploiting the strong interaction between biotin and streptavidin (SA). [33,34] Specifically, we used BL21(DE3) competent Escherichia coli (E. coli) to express a single chain dimer of the MS2 bacteriophage coat protein [35,36] with an inserted AviTag, [33,34] which allowed for the site-specific biotinylation of the VLPs. MS2 VLPs have been shown to be stable for 12 months at 4 °C, [37] and the inserted AviTag was placed in a surface loop that had previously been shown to tolerate a peptide insertion such that the MS2 VLP retains a relatively stable structure.…”

A multivalent Plasmodium falciparum circumsporozoite protein‐based nanoparticle malaria vaccine elicits a robust and durable antibody response against the junctional epitope and the major repeats

“…We subcutaneously inoculated mice ( n = 5) with cPf CSP‐SpyCatcher‐mi3 or SpyCatcher‐mi3 alone (control), each mixed with an equal volume of AddaVax, a vaccine adjuvant consisting of a squalene‐based oil‐in‐water nano‐emulsion. Addavax is similar to MF59, which has been licensed for use in humans, 44,45 and we have used it successfully in our previous work 37,46–48 . A boost was carried out 21 days later.…”

Multivalent S2-subunit Vaccines Provide Broad Protection Against Clade 1 Sarbecoviruses

“…We have previously developed streptavidin-coated VLPs and multivalently presented numerous biotinylated antigens on them as vaccine constructs, including the Zika virus envelope protein domain III 23 , In uenza virus hemagglutinin 24 , various sarbecovirus S proteins 12,25 , and the SARS-CoV-2 S2 subunit. 14 The core of the VLP is the bacteriophage MS2 coat protein, which self-assembles from 90 MS2 homodimers.…”