mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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.
Pardi and colleagues report on a vaccine platform in which purified, antigen-encoding, nucleoside-modified mRNA is encapsulated in lipid nanoparticles. Immunization with this vaccine elicits potent T follicular helper cell, germinal center B cell, and protective, neutralizing antibody responses.
Summary
SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4
+
and CD8
+
T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection
in vitro
. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.
A relationship between fear of crime and the racial composition of place has been widely assumed but seldom tested. Interviews conducted with a random sample of adults residing in a major state capital in the early months of 1994‐at the height of a media‐driven panic about violent crime‐are used to test the proposition that as the percentage of blacks in one's neighborhood increases, so too will the fear of crime. We use objective and perceptual measures of racial composition, and we examine the effects of racial composition and minority status on fear of crime for black and white respondents. We distinguish between perceived safety or risk of victimization and fear, with the former used as an intervening variable in path models of fear of crime. Results show that actual racial composition has no consequence for the fear of crime when other relevant factors are controlled. Perceived racial composition is significant for fear among whites, but not among African‐Americans. In particular, the perception that one is in the racial minority in one's neighborhood elevates fear among whites but not among blacks. All effects of perceived racial composition on fear are indirect and mediated by the perception of risk of crime.
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