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Ramos-Sevillano, Elisa, Ercoli, Giuseppe, Guerra-Assunção, José Afonso, Felgner, Philip, Ramiro de Assis, Rafael, Nakajima, Rie, Goldblatt, David, Tetteh, Kevin Kweku Adjei, Heyderman, Robert Simon, Gordon, Stephen 
ORCID: https://orcid.org/0000-0001-6576-1116, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 and Brown, Jeremy Stuart
(2021)
'Protective Effect of Nasal Colonisation with ∆cps/piaA and ∆cps/proABCStreptococcus pneumoniae Strains against Recolonisation and Invasive Infection'. Vaccines, Vol 9, Issue 3, p. 261.
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vaccines-09-00261 - DFerreira.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
RATIONALE
Nasopharyngeal administration of live virulence-attenuated strains is a potential novel preventative strategy. One target for creating reduced virulence strains is the capsule, but loss of the capsule reduces the duration of colonisation in mice which could impair protective efficacy against subsequent infection.
OBJECTIVES
To assess protective efficacy of nasopharyngeal administration of unencapsulated strains in murine infection models.
METHODS
Strains containing locus deletions combined with the virulence factors (reduces colonisation) or (no effect on colonisation) were constructed and their virulence phenotypes and ability to prevent recolonisation or invasive infection assessed using mouse infection models. Serological responses to colonisation were compared between strains using ELISAs, immunoblots and 254 protein antigen array.
MEASUREMENTS AND MAIN RESULTS
The and strains were strongly attenuated in virulence in both invasive infection models and had a reduced ability to colonise the nasopharynx. ELISAs, immunoblots and protein arrays showed colonisation with either strain stimulated weaker serological responses than the wild type strain. Mice previously colonised with these strains were protected against septicaemic pneumonia but, unlike mice colonised with the wild type strain, not against recolonisation.
CONCLUSIONS
Colonisation with the and strains prevented subsequent septicaemia, but in contrast, to published data for encapsulated double mutant strains they did not prevent recolonisation with . These data suggest targeting the locus is a less effective option for creating live attenuated strains that prevent infections.
| Item Type: | Article |
|---|---|
| Subjects: | WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 202 Pneumonia (General or not elsewhere classified) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified) WV Otolaryngology > WV 100 General works |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW) |
| Digital Object Identifer (DOI): | https://doi.org/10.3390/vaccines9030261 |
| Depositing User: | Julie Franco |
| Date Deposited: | 22 Apr 2021 15:21 |
| Last Modified: | 22 Apr 2021 15:21 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/17655 |
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