Biology subjects

Pierson, T.

Publications and source records attributed to Pierson, T..

3 recordsLinked to original sources

bioRxiv2022

An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection

Zika virus (ZIKV), an arbovirus transmitted by mosquitoes, was identified as a cause of congenital disease during a major outbreak in the Americas in 2016. Vaccine design strategies relied on limited available isolate sequence information due to the rapid response necessary. The first-generation ZIKV mRNA vaccine, mRNA-1325, was initially generated and, as additional strain sequences became available, a second mRNA vaccine, mRNA-1893, was developed. Herein, we compared the immune responses following mRNA-1325 and mRNA-1893 vaccination and reported that mRNA-1893 generated comparable neutralizing antibody titers to mRNA-1325 at 1/20th of the dose and provided complete protection from ZIKV challenge in non-human primates. In depth characterization of these vaccines indicated that the observed immunologic differences could be attributed to a single amino acid residue difference that compromised mRNA-1325 virus-like particle formation.

immunology↗

bioRxiv2022

Zika virus spreads through infection of lymph node-resident macrophages

Zika virus (ZIKV) is an arthopod-vectored flavivirus that disseminates from the infection site into peripheral tissues, where it can elicit virus-induced pathology. To move through the body, ZIKV is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, multiple distinct steps during viral spread culminate in peripheral tissue infection, and the timing and mechanisms underlying mobile immune cell shuttling of virus remain unclear. To understand the very early steps in ZIKV dissemination from the skin, we kinetically and spatially mapped ZIKV-infected lymph nodes (LNs), an intermediary stop en route to the blood. Contrary to dogma, migratory immune cells were not required for large quantities of virus to reach the LN or blood. Instead, ZIKV rapidly infected a subset of immobile macrophages in the LN, which shed virus through the lymphatic pathway into the blood. Importantly, infection of LN macrophages alone was sufficient to initiate viremia. Together, our studies indicate that sessile macrophages that live and die in the LN contribute to initial ZIKV spread to the blood. These data build a more complete picture of ZIKV movement through the body and identify an alternate anatomical site for potential antiviral intervention. HighlightsO_LIZIKV infects and replicates in distinct LN macrophage populations C_LIO_LILN macrophage infection results in infectious virus in the blood C_LIO_LIVirus reaches the blood in the absence of DC migration or monocyte infection C_LIO_LINodal macrophage infection does not sustain viremia or induce morbidity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=74 HEIGHT=200 SRC="FIGDIR/small/508424v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@121bc33org.highwire.dtl.DTLVardef@1caf24borg.highwire.dtl.DTLVardef@e94a08org.highwire.dtl.DTLVardef@1fb6f62_HPS_FORMAT_FIGEXP M_FIG Caption: ZIKV infects lymph node macrophages, which shed infectious virus into the lymph and then blood. C_FIG

microbiology↗

bioRxiv2020

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates

Development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we found that mRNA-LNP immunization compared to protein immunization elicited either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope (prM-E) or HIV-1 Env gp160 induced durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 g were immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

immunology↗