Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes

Abstract

In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a single oral immunization with a mutant strain with an insertion of the chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene decreased the number of salmonellae in each tissue sample 5 days after oral challenge with virulent S. Typhimurium at weeks 26 and 54 postimmunization. These data suggested that an oral immunization with the ClpP-or Lon-disrupted S. Typhimurium strain could provide long-term protection against oral challenge with virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella (NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium and S. enterica serovar Enteritidis harbouring stable in-frame markerless deletions of the clpP-lon-sulA (suppressor of lon), lonsulA or lon-msbB (acyltransferase) genes. Amongst these orally administered vaccine candidates, those with the lon-sulA gene deletion mutants of S. Typhimurium and S. Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis could be a promising cross-protective NTS live vaccine candidate for practical use in humans.

Short-chain fatty acids bind to apoptosis-associated speck-like protein to activate inflammasome complex to prevent Salmonella infection

“…SPI-1 knock-down bacteria were constructed with an in-frame deletion of sipB , a transcriptional activator of SPI-1. An Flp recombination target (FRT)-flanked chloramphenicol-resistant marker cassette (KD3) fragment was amplified using the primers 5′-GTGTAGGCTGGAGCTGCTTC-3′ (forward) and 5′-ATGGGAATTAGCCATGGTCC-3′ (reverse) [ 56 ], and the PCR products were inserted into pGFPmut 3.1 (Clonetech, cat. no.…”

Antimicrobial resistance and management of invasive Salmonella disease

“…Although we do not have a WHO recommended vaccine for prevention of iNTS disease there have been a number of initiatives that have led to the development of promising vaccine candidates that may play a major role in management and control of iNTS disease in endemic areas [65,66]. …”

Live attenuated vaccines for invasive Salmonella infections

“…Studies that have examined cross-protection elicited by Salmonella vaccines have shown mixed results with some reports describing cross-protection against heterologous challenge organisms and others reporting no protection. [24, 99– 103] Similarly, volunteer studies have shown that immune responses generated by live S . Typhi vaccines are cross-reactive with other Salmonella serovars but it is not yet known whether these responses would be protective.…”