bioRxiv Science⌕ Search

Biology subjects

Lafleur, J. E.

Publications and source records attributed to Lafleur, J. E..

3 recordsLinked to original sources

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

immunology↗

Paraoxonase and acylated homoserine lactones in urine from patients with urinary tract infections--relationship to microbial diversity by 16S rRNA gene sequencing

Paraoxonase (PON) comprises a trio of mammalian enzymes that have been reported to have a number of roles including the inhibition of bacterial virulence and biofilm formation by microorganisms that quorum sense with acylated homoserine lactones (AHLs). PON have previously been reported to inhibit P. aeruginosa biofilm formation in mammalian airways and skin. An innate immune role for PON in urinary tract infection has not previously been reported. We performed western blots for PON1 in urine from patients with urinary tract infection (UTI), and also tested UTI urine for the presence of AHLs using a cellular reporter system. Urine sample microbiota was assessed through sequencing of the 16S rRNA marker gene. We report here that PON1 was not found in the urine of control subjects, however, in patients with UTI, PON1 was associated with the presence of E. coli in urine. AHLs, but not PON, were found in the bulk urine of those with P. aeruginosa UTI. Microbial consortia of PON positive UTI urine was found to be distinct from PON negative UTI urine; differentially over-represented bacteria in PON positive samples included a number of environmental opportunists. We hypothesize that PON may inhibit the quorum sensing activity of AHLs in UTI, as has previously described in skin and airways.

microbiology↗

Paraoxonase and acylated homoserine lactones in urine from patients with urinary tract infections

Paraoxonases are mammalian enzymes that have a number of roles including the inhibition of bacterial virulence and biofilm formation by microorganisms that quorum sense with acylated homoserine lactones. Paraoxonases have previously been reported to inhibit P. aeruginosa biofilm formation in mammalian airways and skin. An innate immune role for paraoxonases in urinary tract infection has not previously been reported. We performed western blots for paraoxonase1 in urine from patients with urinary tract infection; we also tested urinary tract infection urine for the presence of acylated homoserine lactones using a cellular reporter system. We report here that paraoxonase1 was not found with our western blot assay in the urine of normal control patients; in those with urinary tract infection, paraoxonase1 was associated with E. coli UTI. Acylated homoserine lactones, but not paraoxonases, were found in the bulk urine of those with P. aeruginosa urinary tract infection. We hypothesize that paraoxonase may play a similar innate immune role in infected urine as has previously described in skin and airways.

immunology↗