Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters

Abstract The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies

Positivity of fecal samples harvested from ten rabid <i>Parastrellus hesperus</i> carcasses and tested at time 0 and after 24 hours at ambient conditions.

Positivity of fecal samples harvested from ten rabid Parastrellus hesperus carcasses and tested at time 0 and after 24 hours at ambient conditions.</p

Using the LN34 assay, rabies virus was detected in the brainstem, mouth swab, and feces of rabid bat carcasses.

Values are Ct means of three replicates, with standard deviations in parentheses. BA = β-actin.</p

Positivity and amplification success of two RABV fecal samples declined at dilutions exceeding 1:10.

Dilutions positive for rabies virus are in bold; LN34 is mean Ct over three replicates for the LN34 assay, with standard deviation in parentheses; BA is Ct for the β-actin assay; # Amp is the number of successful amplifications; and, the positive control was a synthetic sequence provided by the Center for Disease Control. RABV fecal 1 was from a Tadarida brasiliensis and RABV fecal 2 was from an Eptesicus fuscus.</p

qPCR results for sample type comparison, time tests, and pooling experiment.

qPCR results for sample type comparison, time tests, and pooling experiment.</p

Positivity of fecal samples harvested from rabid bat carcasses and tested at 24, 48, and 72 hours at ambient conditions.

At 72 hours, at least one replicate was positive for 4 of 6 samples (a) and all three replicates were positive for 3 of 6 samples (b). Bat species tested included Eptesicus fuscus (n = 1), Tadarida brasiliensis (n = 3), Antrozous pallidus (n = 1), and Lasiurus xanthinus (n = 1).</p

Standard curve regression coefficients, quantification reliability [PCR efficiency and limit of quantification (LOQ)], and sensitivity estimates [limit of detection (LOD) via probit modeling].

Estimates of LOD are predicted assuming n replicates per sample (i.e., effective LOD), with 95% confidence intervals in brackets. The bolded row highlights the effective LOD reflecting the proposed number of qPCR replicates to run for regular screening.</p

Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients

The Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2. Vaccination decreased the infectious viral load, but not the amount of viral RNA. Furthermore, vaccinees with asymptomatic infections had significantly higher levels of anti-spike IgA in their nasal secretions compared to unvaccinated individuals with asymptomatic infections. Thus, vaccination may decrease the transmission risk of Delta, and perhaps other variants, despite not affecting the amount of viral RNA measured in nasopharyngeal swabs

Superior Conjugative Plasmids Delivered by Bacteria to Diverse Fungi

Fungi are nature’s recyclers, allowing for ecological nutrient cycling and, in turn, the continuation of life on Earth. Some fungi inhabit the human microbiome where they can provide health benefits, while others are opportunistic pathogens that can cause disease. Yeasts, members of the fungal kingdom, have been domesticated by humans for the production of beer, bread, and, recently, medicine and chemicals. Still, the great untapped potential exists within the diverse fungal kingdom. However, many yeasts are intractable, preventing their use in biotechnology or in the development of novel treatments for pathogenic fungi. Therefore, as a first step for the domestication of new fungi, an efficient DNA delivery method needs to be developed. Here, we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida auris. To create our superior plasmids, derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions, as well as some unintentional mutations. Specifically, a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to yeasts. In addition, we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic cassettes. Finally, we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent, with important applications for the development of next-generation antifungal therapeutics

Anti‐ableist language is fully compatible with high‐quality autism research: Response to Singer et al. (2023)

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