Live attenuated nephropathogenic infectious bronchitis virus vaccine provides broad cross protection against new variant strains

Abstract

Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors. Such increased antigen production and simultaneous attenuation were expected to elicit protective immunity against Shigella strains of heterologous serotypes. Thus, the vaccine potential of this mutant was tested in two guinea pig models of shigellosis. Animals vaccinated in the left eye showed fewer symptoms upon subsequent challenge via the right eye, and even survived subsequent intestinal challenge. In addition, oral vaccination effectively induced production of immunoglobulins without severe side effects, again protecting all animals against subsequent intestinal challenge with S. dysenteriae type 1 or S. sonnei strains. Antibodies against common virulence proteins and the O-antigen of S. flexneri 2a were detected by immunofluorescence microscopy. Reaction of antibodies with various strains, including enteroinvasive Escherichia coli, suggested that common virulence proteins induced protective immunity against a range of sero-types. Therefore, vaccination is expected to cover not only the most prevalent serotypes of S. sonnei and S. flexneri 2a, but also various Shigella strains, including S. dysenteriae type 1, which produces Shiga toxin. Author summary An ideal vaccine should show a broad range of protective efficacy against all serotypes of a particular pathogen. Variations in the structural lipopolysaccharide "O"-antigen mean PLOS Neglected Tropical Diseases | https://doi.

Factors influencing the outcome of infectious bronchitis vaccination and challenge experiments

“…Whilst 1-day-old vaccination has been used in some studies (Toro & Fernandez, 1994;Lin et al, 2005;Martin et al, 2007), vaccination is frequently delayed until approximately 2 weeks (Endo-Munoz & Faragher, 1989;Lambrechts et al, 1993;Liu et al, 2009;Meir et al, 2012;Gelb et al, 2013), 3 weeks (Lim et al, 2012), or even as late as 5 weeks of age (Rosenberger et al, 1976). It is not easy to understand why this might be the case, except that it may be intended to mimic the age at which specific vaccines are applied in the field.…”

“…route is commonly practiced. However, this is by far the most common route of vaccination used in experimental studies (Winterfield, 1968;Ratanasethakul & Cumming, 1983;Alvarado et al, 2003;Joiner et al, 2007;Matthijs et al, 2008;Terregino et al, 2008;Wood et al, 2009;Lim et al, 2012;Meir et al, 2012). Whilst this enables an accurate estimation of the virus dose applied to each chick, the relationship to the field situation is more difficult to establish.…”

“…Whilst al-Tarcha et al (Winterfield, 1968;Rosenberger et al, 1976;Gelb et al, 1991;Nix et al, 2000;Alvarado et al, 2003;Lim et al, 2012;Meir et al, 2012). In a sequential study, Gough & Alexander (1979) challenged birds at intervals from 1 week to 32 weeks p.v.…”

“…Again there is quite good agreement, and is seems common to give log 10 4.0 to log 10 5.0 EID 50 per chick when challenge is via the o.n. route (Toro & Fernandez, 1994;Alvarado et al, 2003;Joiner et al, 2007;Martin et al, 2007;Shimazaki et al, 2008;De Wit et al, 2011b, 2013Lim et al, 2012). In most of his work, Winterfield used a lower dose of approximately log 10 3.0 EID 50 /bird (Winterfield, 1968) and this dose was also used by Terregino et al (2008).…”

“…Generally, protection is assessed at between 5 and 7 d.p.c. (Ratanasethakul & Cumming, 1983;Gelb et al, 1991;Cook et al, 1999;Alvarado et al, 2003;Terregino et al, 2008;Jackwood et al, 2009;Lim et al, 2012;De Wit et al, 2013), although Darbyshire & Peters (1985) sampled 4 d.p.c. Lambrechts et al (1993) investigated levels of cross-protection in the respiratory tract at 1, 3, 5, 7 and 9 days following aerosol challenge with the B1648 IBV variant in chicks that had been vaccinated with different IBV vaccines.…”