Immunity induced by vaccination with recombinant influenza B virus neuraminidase protein breaks viral transmission chains in guinea pigs in an exposure intensity-dependent manner (preprint)

Mucosal vaccines and vaccines that block pathogen transmission are under-appreciated in vaccine development. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that blocking viral transmission is an important attribute of efficient vaccines. Here, we investigated if recombinant influenza virus neuraminidase (NA) vaccines delivered at a mucosal site could protect from onward transmission of influenza B viruses in the guinea pig model. We tested four different scenarios in which sequential transmission was investigated in chains of four guinea pigs. The variables tested included a low and a high viral inoculum (10 4 vs 10 5 plaque forming units) in the initial donor guinea pig and variation of exposure/cohousing time (1 day vs 6 days). In three out of four scenarios – low inoculum-long exposure, low inoculum-short exposure and high inoculum-short exposure – transmission chains were efficiently blocked. Based on this data we believe an intranasal recombinant NA vaccine could be used to efficiently curtail influenza virus spread in the human population during influenza epidemics. Importance Vaccines that can slow respiratory virus transmission in the population are urgently needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Here we describe how a recombinant neuraminidase-based influenza virus vaccines reduces transmission in vaccinated guinea pigs in an exposure-intensity based manner.

SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months (preprint)

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.

Seroconversion of a city: Longitudinal monitoring of SARS-CoV-2 seroprevalence in New York City (preprint)

By conducting a retrospective, cross-sectional analysis of SARS-CoV-2 seroprevalence in a sentinel group (enriched for SARS-CoV-2 infections) and a screening group (representative of the general population) using >5,000 plasma samples from patients at Mount Sinai Hospital in New York City (NYC), we identified seropositive samples as early as in the week ending February 23, 2020. A stark increase in seropositivity in the sentinel group started the week ending March 22 and in the screening group in the week ending March 29. By the week ending April 19, the seroprevalence in the screening group reached 19.3%, which is well below the estimated 67% needed to achieve community immunity to SARS-CoV-2. These data potentially suggest an earlier than previously documented introduction of SARS-CoV-2 into the NYC metropolitan area.

A serological assay to detect SARS-CoV-2 seroconversion in humans (preprint)

SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.