Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination

Abstract

Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins2,3. Here, we demonstrate that a single low-dose intradermal immunization with lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.

Exclusive and Common Subsets of Zika Virus Polyprotein Mutants

“…There are other, specific immunological human host factors that affect the Zika virus. Neutralizing antibodies against the prM precursor membrane protein (prM) and envelope E protein have been reported [10][11][12]. The prM and E proteins initially exist as precursors within the structural domain of the polyprotein.…”

Zika Virus: Current Status, Protective Vaccine Trials, and Antiviral Treatment Alternatives

“…Tek seferde düşük doz intradermal aşılama ile fare ve rhesus maymunlarında yüksek düzey nötralizan antikor yanıtı ile koruyucu etki gösterdiği bildirilmiştir (56) .…”

Polyamine‐Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery

“…[1][2][3][4] Unlike protein-based biologics, mRNA co-opts natural biological processes to express proteins and thereby achieve a desired therapeutic effect. [5][6] In contrast to DNA, however, mRNA does not need to enter the nucleus to be functional, which allows for transfection of non-dividing cells with potentially high efficiency.…”

“…On the other hand, the synthetic mRNA utilized in this study contains pseudouridine-and 5-methylcytidinesubstituted nucleotides along with a poly A tail at the 3′ end (120 adenosine residues) for optimal mRNA expression, which has been demonstrated in previous studies. [1][2]20] Since each PABP protein is known to bind a continuous stretch of 12 adenosine residues, each mRNA molecule is theoretically able to bind a maximum of ten PABP proteins. [21] Therefore, we first tested three different molar ratios of PABP to mRNA (2:1, 10:1 and 50:1) and subsequently encapsulated them with seven different polyamines.…”

“…[8][9] These advantages enable the potential treatment of a broad spectrum of diseases, many of which cannot be addressed with current technologies. [1][2] Nevertheless, inefficient transfection of exogenous mRNA remains a key barrier to broad applications of mRNA-based drugs. [10] Endogenous mRNA associates with specific proteins at different stages when trafficking from the nucleus to cytoplasmic ribosomes for maximal protein production.…”