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R Curtiss

Publications and source records attributed to R Curtiss.

At least 37 records · Page 2Linked to original sources

Cell-specific proteins synthesized by Salmonella typhimurium.

Studies of the proteins synthesized by Salmonella typhimurium during growth within tissue culture cells have previously focused on a single cell type. In the present study we examine the different protein patterns exhibited by S. typhimurium during growth within three different cell types relevant to those it would encounter throughout the course of a natural infection, including intestinal epithelial cells (Intestine-407), macrophages (J774.A, rat bone marrow-derived macrophages, and mouse bone marrow-derived macrophages), and liver cells (NMuLi). Side-by-side comparisons reveal that S. typhimurium responds to these different cellular environments with specific patterns of protein synthesis unique to each cell type. The numbers of proteins detected in each cell line are as follows: 142 proteins in Intestine-407, of which 58 appear to be unique to growth within this cell line; 413 proteins in J774.A, of which 157 appear to be unique; 260 proteins in rat bone marrow-derived macrophages, of which 40 appear to be unique; 336 proteins in mouse bone marrow-derived macrophages, of which 113 appear to be unique; and 183 proteins in NMuLi, of which 91 appear to be unique.

Animals↗

A live recombinant avirulent oral Salmonella vaccine expressing pneumococcal surface protein A induces protective responses against Streptococcus pneumoniae.

A live oral recombinant Salmonella vaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Deltacya Deltacrp mutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Deltaasd mutation was complemented by a plasmid vector possessing the asd+ gene. A portion of the pspA gene from Streptococcus pneumoniae Rx1 was cloned onto a multicopy Asd+ vector. After oral immunization, the recombinant Salmonella-PspA vaccine strain colonized the Peyer's patches, spleens, and livers of BALB/cByJ and CBA/N mice and stimulated humoral and mucosal antibody responses. Oral immunization of outbred New Zealand White rabbits with the recombinant Salmonella strain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on the S. pneumoniae cell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producing Salmonella strain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolate S. pneumoniae WU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2.

Administration, Oral↗

Antitumor mechanisms of attenuated Salmonella typhimurium containing the gene for human interleukin-2: a novel antitumor agent?

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella species are known to naturally track to the liver during active infection. To develop a biological vector for delivery of interleukin-2 (IL-2) to the liver for antitumor purposes, the thi 4550 attenuated strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 and inserted into the attenuated S typhimurium and renamed (thi 4550(pIL-2)]. MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases that were subsequently enumerated after 12 days. We previously have demonstrated that the thi 4550(pIL-2) produces biologically active IL-2 and that a single gavage feeding of 10(7) thi 4550(pIL-2) significantly reduced the number of hepatic metastases when compared with animals fed salmonella lacking the IL-2 gene or nontreated controls. The aims of the current studies were to determine which host effector cell populations were responsible for the antitumor effect seen with thi 4550(pIL-2) by depletion of natural killer (NK), cytotoxic T lymphocytes (CD8+), T helper (CD4+) cells, and Kupffer cells. Multiple experiments were conducted for each host effector cell population depleted. We found a consistent reduction in the mean number of hepatic metastases in animals fed thi 4550(pIL-2) (55.6 metastases; n = 54) when compared with controls (162.3 metastases; n = 53) (P < .0001). Depletion of NK cells and CD8+ T cells significantly inhibited the antitumor effect of thi 4550(pIL-2) (analysis of variance [ANOVA], P < .01). Elimination of CD4+ T cells and Kupffer cells had no significant impact on the antitumor effect of thi 4550(pIL-2) (ANOVA, P value was not significant). Salmonella IL-2 may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies that employs the oral route of administration. Furthermore, both NK cells or CD8+ cells are required for the antitumor effect seen while CD4+ T cells and Kupffer cells do not appear to be as essential.

Adenosarcoma↗

Display of heterologous proteins on the surface of microorganisms: from the screening of combinatorial libraries to live recombinant vaccines.

In recent years there has been considerable progress towards the development of expression systems for the display of heterologous polypeptides and, to a lesser extent, oligosaccharides on the surface of bacteria or yeast. The availability of protein display vectors has in turn provided the impetus for a range of exciting technologies. Polypeptide libraries can be displayed in bacteria and screened by cell sorting techniques, thus simplifying the isolation of proteins with high affinity for ligands. Expression of antigens on the surface of nonvirulent microorganisms is an attractive approach to the development of high-efficacy recombinant live vaccines. Finally, cells displaying protein receptors or antibodies are of use for analytical applications and bioseparations.

Bacterial Proteins↗

Patterns of hepatic and splenic colonization by an attenuated strain of Salmonella typhimurium containing the gene for human interleukin-2: a novel anti-tumor agent.

Currently, there is no effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. A live biological vector was developed for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes. The avirulent and highly immunogenic c4550 strain of Salmonella typhimurium was used to express the IL-2 protein [renamed c4550(pIL-2)]. We have previously demonstrated that the c4550(pIL-2) produces biologically active IL-2 (up to 46.2 IU/ml) and that a single gavage feeding of 10(7) colony forming units (cfu) of c4550(pIL-2) significantly reduced the number of hepatic metastases when compared to animals fed salmonella lacking the IL-2 gene or non-treated controls. The goal of the current studies was to determine the pattern of splenic and hepatic colonization of Salmonella-IL2. Hepatic and splenic colonization was determined following administration of 10(7) cfu of c4550(pIL-2) and c4550(pYA292) via a single gavage feeding to C57BL/6 mice. Five experiments of antibiotic regimen administration were conducted where splenic and hepatic homogenates were cultured after 14 days of parenteral and/or oral antibiotics. The natural history of hepatic and splenic colonization was also determined for animals without antibiotic treatment. Despite administration of various antibiotic regimens using different routes, eradication of salmonella with and without IL-2 was not achieved. Salmonella, however, was not cultured from hepatic and splenic tissue at 4 months after a single gavage feeding of salmonella with no specific treatment. In conclusion, oral administration of c4550(pIL-2) may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies. Antibiotics do not accelerate eradication of this bacteria and it appears that c4550(pIL-2) follows the natural pathophysiological of salmonella infection in which eradication from the splenic and hepatic tissue occurs over a period of 2-4 months.

Animals↗

Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3.

Ovarian ZP3, the primary sperm receptor, is a major glycoprotein of mouse zona pellucida (ZP). Because antibodies raised against ZP3 block sperm-egg interaction, ZP3 has been considered a candidate immunogen in the development of a contraceptive vaccine. This study explored the possibility of using an attenuated Salmonella typhimurium vaccine strain expressing recombinant ZP3 to elicit an antibody response and infertility in mice. A cDNA sequence generated by the polymerase chain reaction encoding 342 amino acid residues (23-364) of the mouse (m)ZP3 was cloned into an Asd+ vector. An avirulent Salmonella vaccine strain stably expressed the ZP3 polypeptide and colonized the internal organs of mice after oral inoculation. Oral immunization of female BALB/c mice with the recombinant Salmonella vaccine strain expressing mZP3 induced significant levels of anti-native ZP IgG antibodies in serum and IgA antibodies in vaginal secretions. The IgG antibodies thus induced also bound to ZP in vivo. When mated with males, 3 of 6 females immunized with the recombinant Salmonella were infertile. In contrast, none of the mice that received Salmonella containing the vector plasmid produced antibodies to ZP and all were fertile. No ovarian inflammation was observed in the immunized mice at autopsy. The results suggest a potential oral contraceptive vaccine to control populations of rodent vectors of disease and to induce reversible infertility in humans.

Animals↗

An altered rpoS allele contributes to the avirulence of Salmonella typhimurium LT2.

Virulent Salmonella typhimurium strains differ from the attenuated laboratory strain LT2 at the rpoS locus. It was previously shown that the rpoS gene in strain LT2 contains a rare UUG start codon (I. S. Lee, J. Lin, H. K. Hall, B. Bearson, and J. W. Foster, Mol. Microbiol. 17:155-167, 1995). This difference is responsible for the inability of LT2 to display a sustained log-phase acid tolerance response. We show that the altered rpoS allele (rpoS(LT2)) also affects the stationary-phase acid tolerance response in Salmonella. By transducing the rpoS(LT2) allele into virulent strain backgrounds and crossing wild-type rpoS allele into strain LT2, we demonstrate that the rpoS(LT2) allele contributes to the attenuation of strain LT2. We examined the effect of the rpoS allele on invasion and found that the rpoS status of the cell had no effect on the ability of the strains to invade intestinal epithelial cells in tissue culture. Enumeration of bacteria from tissues of infected mice indicated that the presence of the rpoS(LT2) allele affected the ability of S. typhimurium to reach the liver and spleen and to persist in several tissues at 6 days postinfection. This is likely due, at least in part, to a decrease in spv gene expression in these mutants. We demonstrate that strains containing the rpoS(LT2) allele are not only sensitive to pH 3.0 (acid stress) but are also sensitive to the DNA-damaging agent methyl methanesulfonate. However, these strains appear to survive stationary-phase and oxidative stresses as well as strains containing a wild-type rpoS allele. Despite an increased sensitivity to acid stress and DNA damage, strains containing either an rpoS-null mutation or the rpoS(LT2) allele survived in J774 cells and bone marrow-derived macrophages as well as did otherwise isogenic strains with a wild-type rpoS allele.

Acids↗

Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 delta crp and delta cdt deletion mutants.

S. typhimurium SL1344 and UK-1 mutants with deletions of the crp (cyclic AMP receptor protein) and cdt (colonization of deep tissues) genes have been constructed and characterized, and their levels of virulence and immunogenicity have been determined for BALB/c mice. All Crp- Cdt- and Crp+ Cdt- mutants were avirulent, as mice survived oral doses of 10(9) cells without illness. All the mutants colonized the gut-associated lymphoid tissue efficiently, but capacities to colonize deeper tissues, such as those of the spleen and liver, and blood were significantly reduced for the Crp- Cdt- and Crp+ Cdt- mutants compared with the Crp- Cdt+ mutant and the wild-type parent strain. The Crp- Cdt- and Crp+ Cdt- SL1344 strains induced complete protection, as all mice immunized with the mutants survived challenge with approximately 10(4) times the 50% lethal dose of the wild-type SL1344 strain. The Crp- UK-1 strain was least attenuated yet induced the highest level of protective immunity against challenge with the wild-type UK-1 strain. The Crp+ Cdt- and Crp- Cdt- strains, although totally attenuated, differed in immunogenicity to challenge with the highly virulent UK-1 parent, with the apparently hyperattenuated Crp- Cdt- strain inducing a lower level of protective immunity than the Crp+ Cdt- strain. Nevertheless, these UK-1 Crp- Cdt- and Crp+ Cdt- strains induced complete protective immunity to challenge with the less-virulent SL1344 wild-type strain. Taken collectively, the results indicate that the attenuation of a highly virulent S. typhimurium strain can yield a vaccine that induces excellent protective immunity to challenge with less-virulent S. typhimurium strains.

Animals↗

Role of sigma factor RpoS in initial stages of Salmonella typhimurium infection.

The sigma factor RpoS mediates the stationary-phase expression of a large group of genes, including those involved in resistance to a variety of environmental stresses, such as starvation, oxidation, and low pH. In addition, RpoS has been shown to regulate Salmonella virulence. In Salmonella typhimurium, RpoS controls the expression of the Salmonella plasmid virulence (spv) genes, which are required for systemic infection. However, the mechanism by which RpoS affects the pathogenicity of Salmonella remains incompletely defined. In this study, we focused on the ability of rpoS to affect the early stages of the infection process of S. typhimurium. An rpoS mutant of S. typhimurium exhibited wild-type abilities to attach to and invade Int-407 cells and J774 macrophage-like cells. In addition, rpoS did not affect the intracellular survival of S. typhimurium in either J774 macrophage-like cells or rat bone marrow-derived macrophages. However, the rpoS mutant demonstrated a decreased ability to colonize murine Peyer's patches after oral inoculation than its wild-type virulent parent strain showed. In addition, virulence plasmid-cured derivatives of the rpoS mutant were recovered in lower numbers from murine Peyer's patches than were plasmid-cured derivatives of the isogenic wild-type S. typhimurium. This indicates that RpoS regulation of chromosomally encoded genes is important for colonization of the gut-associated lymphoid tissue (GALT) by S. typhimurium. Microscopic analysis of histological sections taken from Peyer's patches after peroral infection of mice showed that, unlike its wild-type virulent parent strain, the isogenic rpoS mutant did not destroy the follicle-associated epithelium of the GALT. Furthermore, the rpoS mutant demonstrated a decreased ability to adhere to histological sections of murine Peyer's patches than its wild-type parent showed. Our data provide evidence for a role of RpoS in the interaction of Salmonella with cells of the GALT, specifically the Peyer's patches. This implicates the involvement of rpoS in the initial stages of systemic infection by Salmonella as opposed to infection leading to gastroenteritis.

Animals↗

Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asd-balanced lethal vector system.

Attenuated Salmonella typhi organisms which express genes encoding protective antigens of other pathogens have been developed for use as experimental oral vaccines. A delta asd S. typhi strain attenuated by deletions in cya, crp, and cdt which contains hepatitis B core (HBc) and pre-S genes encoded on an Asd+ pBR-based plasmid vector was constructed. Healthy adult volunteers ingested a single dose of 5 x 10(5) to 5 x 10(8) CFU of strain chi4073 (delta cya delta crp delta cdt S. typhi Ty2), 6 x 10(7) or 1 x 10(9) CFU of strain chi4632(pYA3149), a further derivative of chi4073 deleted in asd and containing the Asd+ vector without the HBc-pre-S fusion, or 3 x 10(7) or 7 x 10(8) CFU of strain X4632(pYA3167), a derivative containing the vector with the HBc-pre-S fusion. Chi4073 was generally well tolerated by 22 volunteers. No volunteer had fever or positive blood cultures; 4 of 22 volunteers shed vaccine organisms in the stool in the first 48 h only. Two of 18 volunteers who received one of the plasmid-containing derivatives of chi4073 developed low-grade fevers on day 10 or 12 after ingestion. One of these volunteers had positive blood cultures on days 7 and 8. Seven of these 18 volunteers had vaccine organisms detected in their stools in the first 48 h only. Most volunteers developed S. typhi-specific serum responses and developed S. typhi-specific antibody-secreting cells. However, no volunteer developed serum antibody to hepatitis pre-S or pre-S-specific antibody-secreting cells. Although the parent strain chi4073 was well tolerated, induced immunoglobulin G seroconversion to S. typhi lipopolysaccharide in 80 to 100% of vaccinees and stimulated specific IgA-secreting lymphocytes in 80 to 100% of vaccinees given a single oral dose of 2 x 10(7) and 5 x 10(8) CFU, chi4073 derivatives containing the Asd+ vector with and without sequences encoding the HBc-pre-S fusion caused occasional febrile reactions at high doses and did not stimulate detectable immune responses to hepatitis B antigens.

Adult↗

Specific detection of Salmonella typhimurium proteins synthesized intracellularly.

Studies of the proteins Salmonella typhimurium synthesizes under conditions designed to more closely approximate the in vivo environment, i.e., in cell and tissue culture, are not easily interpreted because they have involved chemical inhibition of host cell protein synthesis during infection. The method which we have developed allows specific labeling of bacterial proteins without interfering with host cell metabolic activities by using a labeled lysine precursor which mammalian cells cannot utilize. We have resolved the labeled proteins using two-dimensional electrophoresis and autofluorography. We were able to detect 57 proteins synthesized by S. typhimurium during growth within a human intestinal epithelial cell line. Of the 57 proteins detected, 34 appear to be unique to the intracellular environment, i.e., they are not seen during growth of the bacteria in tissue culture medium alone. Current (and future) efforts are directed at organizing the 34 proteins into known stress response groups, determining the cellular locations of the proteins (outer or inner membrane, etc.), and comparing the pattern of proteins synthesized within an intestinal epithelial cell to the pattern synthesized during growth within other tissues.

Autoradiography↗

Unique chromosomal regions associated with virulence of an avian pathogenic Escherichia coli strain.

The avian pathogenic Escherichia coli strain (chi)7122 (serotype O78:K80:H9) causes airsacculitis and colisepticemia in chickens. To identify genes associated with avian disease, a genomic subtraction technique was performed between strain (chi)7122 and the E. coli K-12 strain (chi)289. The DNA isolated using this method was found only in strain (chi)7122 and was used to identify cosmid clones carrying unique DNA from a library of (chi)7122 that were then used to map the position of unique DNA on the E. coli chromosome. A total of 12 unique regions were found, 5 of which correspond to previously identified positions for unique DNA sequence in E. coli strains. To assess the role each unique region plays in virulence, mutants of (chi)7122 were constructed in which a segment of unique DNA was replaced with E. coli K-12 DNA by cotransduction of linked transposon insertions in DNA flanking the unique sequence. The resulting replacement mutants were assessed for inability to colonize the air sac and cause septicemia in 2-week-old white Leghorn chickens. Two mutants were found to be avirulent when injected into the right caudal air sac of 2-week-old chickens. One avirulent mutant, designated (chi)7145, carries a replacement of the rfb locus at 44 min, generating a rough phenotype. The second mutant is designated (chi)7146, and carries a replacement at position 0.0 min on the genetic map. Both mutants could be complemented to partial virulence by cosmids carrying sequences unique to (chi)7122.

Animals↗

A continuous epitope from transmissible gastroenteritis virus S protein fused to E. coli heat-labile toxin B subunit expressed by attenuated Salmonella induces serum and secretory immunity.

Antigenic site D from the spike protein of transmissible gastroenteritis virus (TGEV), which is a continuous epitope critical in neutralization, has been expressed as a fusion protein with E. coli heat-labile toxin B subunit (LT-B) in attenuated S. typhimurium. Synthetic peptides containing the sequence of site D induced TGEV neutralizing antibodies when inoculated subcutaneously in both rabbits and swine. A synthetic oligonucleotide encoding residues 373-398 of TGEV S protein, including antigenic site D, was cloned in frame with the 3' end of LT-B gene, into a plasmid used to transform S. typhimurium delta asd chi 3730. A collection of 6 recombinant plasmids designated pYALTB-D I-VI encoding LTB-site D fusions with a variable number of site D sequences were selected. Four of the 6 LTB-site D fusion products expressed in S. typhimurium chi 3730 formed oligomers (pentamers) that dissociated at > 70 degrees. S. typhimurium chi 3730 (pYALTB-D) V and VI expressed the oligomer forming products with higher antigenicity. Partially purified LTB-site D fusion product expressed from S. typhimurium chi 3730 (pYALTB-D) V induced anti-TGEV neutralizing antibodies in rabbits. Recombinant vaccine strain S. typhimurium delta cya delta crp delta asd chi 3987 transformed with plasmid pYALTB-D V expressed constitutively products that formed oligomers presumably containing 20 copies of site D, and showed a high stability in vitro. This recombinant strain was orally inoculated in rabbits and induced TGEV specific antibodies in both serum and intestinal secretion.

Amino Acid Sequence↗

Nonrecombinant and recombinant avirulent Salmonella vaccines for poultry.

We have constructed and evaluated a live avirulent Salmonella typhimurium vaccine strain, attenuated by deletion (delta) mutations in genes for adenylate cyclase (cya) and the cAMP receptor protein (crp). Immunization of chicks can preclude Salmonella colonization and invasion of challenged vaccinated chickens when compared with the non vaccinated control. Immunization induces significant cross-protective immunity against various Salmonella serotypes and protects laying hens from transmission of Salmonella in or on eggs following challenge with S. enteritidis or S. typhimurium. Immunization of chicks destined to be breeders and then with a booster immunization at 16-18 weeks of age leads to maternal transfer of immunity to chicks which then can be immunized either orally or by coarse spray to display an enhanced immunity to prevent infection of visceral organs by and shedding of Salmonella. The attenuated S. typhimurium vaccine can be genetically manipulated to express foreign antigens specified by cloned genes from other pathogens. Immunization with such recombinant vaccines not only induces immunity to Salmonella but to infection by the pathogen that supplied the genes specifying the protective antigens expressed by the recombinant vaccine.

Animals↗

Attenuated Salmonella typhimurium containing interleukin-2 decreases MC-38 hepatic metastases: a novel anti-tumor agent.

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. To develop a biological vector for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes, the avirulent and highly immunogenic chi 4550 strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 (renamed pIL-2) and inserted into the attenuated Salmonella typhimurium and renamed [chi 4550 (pIL-2)]. This transformant was found to produced biologically active IL-2 demonstrated by NK cell activation in a 4 hour chromium release cytotoxicity assay. To determine anti-tumor potential, MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases and metastases were subsequently enumerated after 12 days. Statistical significance was determined by ANOVA with Fisher's test for significance. Hepatic metastases enumerated by blinded observers revealed that the mean number of metastases was 106.4 in control mice, 103.7 in mice gavage fed attenuated salmonella without IL-2 [chi 4550(pYA292)], and 44.3 in mice fed the chi 4550(pIL2); (ANOVA: p < 0.01). Culture of livers and spleens in mice administered a single gavage dose of salmonella demonstrated persistent colonization for up to 4 weeks. No observable toxicity was seen to either IL-2 or salmonella. These studies demonstrate that the chi 4550(pIL2) is a novel form of in vivo biotherapy which produces biologically active IL-2 and employs the oral route of administration to stimulate an immune response against malignancy in the liver.

Animals↗

Oral and rectal immunization of adult female volunteers with a recombinant attenuated Salmonella typhi vaccine strain.

An attenuated strain of Salmonella typhi delta(cya) delta(crp-cdt) delta(asd) expressing a gene encoding a hepatitis B virus core-pre-S protein was tested in female adult volunteers for its ability to elicit a systemic and a mucosal immune response. Specifically, our purpose was to evaluate the potential of such a vaccine strain to induce specific secretory immunoglobulin A (sIgA) at genital and rectal surfaces. Oral and rectal routes of immunization were compared: oral immunization induced seroconversion against the bacterial lipopolysaccharide (LPS) in six out of seven volunteers, while after rectal immunization only one out of six volunteers seroconverted against LPS. To our disappointment, the latter volunteer was also the only one who seroconverted against the carried antigen (pre-S1), demonstrating the poor ability of this live vaccine to induce an immune response against the carried antigen. Anti-LPS sIgA was found in both the vaginal and cervical secretions of a volunteer who presented a strong seroconversion after oral immunization (16-fold increase in anti-LPS IgG). Smaller amounts of anti-LPS sIgA were found in the rectal secretions of one orally and one rectally immunized volunteer and in the saliva of three orally and one rectally immunized woman. Our data show for the first time that it is possible to induce specific sIgA in the genital and rectal tracts of women by using an S. typhi vaccine strain.

Administration, Oral↗

Effect of vaccination of hens with an avirulent strain of Salmonella typhimurium on immunity of progeny challenged with wild-Type Salmonella strains.

The avirulent Salmonella typhimurium chi3985 was used to vaccinate white leghorn chickens at 16 and 18 weeks of age, and the effect of maternal antibody on Salmonella colonization of progeny of vaccinated hens was assessed with S. typhimurium F98 or chi3985. Progeny of hens that had been vaccinated at 1 and 3 or 2 and 4 weeks of age with chi3985 were used to determine the effect of maternal immunity on vaccine efficacy. Vaccination of hens induced long-lasting Salmonella-specific antibodies which were transferred into eggs and were detected as immunoglobulin G (IgG) in the egg yolk. Maternal antibody was detected in the progeny of vaccinated birds as IgG and IgA in serum and intestinal fluid, respectively. The titer of maternally transmitted IgG or IgA was highest in the first week of life of the progeny and declined with age. Maternal antibodies prevented colonization of the chicks by S. typhimurium chi3985 and reduced colonization by S. typhimurium F98. Overall, chicks from vaccinated hens had significantly higher antibody responses than did the progeny of nonvaccinated hens after oral infection with Salmonella strains. Maternal antibody reduced the efficacy of vaccination of progeny with chi3985 at 1 and 3 weeks of age. But vaccination at 2 and 4 weeks of age induced excellent protection against challenge with S. typhimurium F98 or S. enteritidis 27A PT 8 in birds from vaccinated hens and in specific-pathogen-free chickens. Vaccination of chickens at 2 and 4 weeks of age has been shown to protect the birds against challenge with homologous and heterologous Salmonella serotypes. A combination of vaccination of adult animals and use of the progeny of vaccinated birds will enhance effective control of Salmonella infections in the poultry industry. This will complement the present control of Salmonella-associated food poisoning caused by Salmonella enteritidis in eggs because the avirulent S. typhimurium vaccine strain chi3985 induced excellent protection against S. enteritidis in chickens.

Animals↗