Search NASA⌕ Search

Engineering topics

McDanal, Charlene

Publications and source records attributed to McDanal, Charlene.

4 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines

All current vaccines for COVID-19 utilize ancestral SARS-CoV-2 spike with the goal of generating protective neutralizing antibodies. The recent emergence and rapid spread of several SARS-CoV-2 variants carrying multiple spike mutations raise concerns about possible immune escape. One variant, first identified in the United Kingdom (B.1.1.7, also called 20I/501Y.V1), contains eight spike mutations with potential to impact antibody therapy, vaccine efficacy, and risk of reinfection. Here in this paper, we show that B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (~2-fold), by serum samples from convalescent individuals and recipients of an mRNA vaccine (mRNA-1273, Moderna) and a protein nanoparticle vaccine (NVX-CoV2373, Novavax). A subset of monoclonal antibodies to the receptor binding domain (RBD) of spike are less effective against the variant, while others are largely unaffected. Lastly, these findings indicate that variant B.1.1.7 is unlikely to be a major concern for current vaccines or for an increased risk of reinfection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine efficacy, sera from spike-immunized mice, nonhuman primates, and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor-binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Here, negative stain electron microscopy revealed a higher percentage of the 1-RBD “up” conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development.

60 APPLIED LIFE SCIENCES↗