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. 2023 Oct 31;11(11):1671.
doi: 10.3390/vaccines11111671.

Induction of Broad Immunity against Invasive Salmonella Disease by a Quadrivalent Combination Salmonella MAPS Vaccine Targeting Salmonella Enterica Serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A

Emily M Boerth  1 , Joyce Gong  1 , Becky Roffler  1 , Claudette M Thompson  1 , Boni Song  1 , Sasha F Malley  1 , Angelika Hirsch  1 , Calman A MacLennan  2 , Fan Zhang  1 , Richard Malley  1 , Ying-Jie Lu  1
Affiliations

Induction of Broad Immunity against Invasive Salmonella Disease by a Quadrivalent Combination Salmonella MAPS Vaccine Targeting Salmonella Enterica Serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A

Emily M Boerth et al. Vaccines (Basel). .

Abstract

Bloodstream infections in low- and middle-income countries (LMICs) are most frequently attributed to invasive Salmonella disease caused by four primary serovars of Salmonella enterica: Typhi, Paratyphi A, Typhimurium, and Enteritidis. We showed previously that a bivalent vaccine targeting S. Typhi and S. Paratyphi A using a Multiple Antigen-Presenting System (MAPS) induced functional antibodies against S. Typhi and S. Paratyphi. In the current study, we describe the preclinical development of a first candidate quadrivalent combination Salmonella vaccine with the potential to cover all four leading invasive Salmonella serotypes. We showed that the quadrivalent Salmonella MAPS vaccine, containing Vi from S. Typhi, O-specific Polysaccharide (OSP) from S. Paratyphi A, S. Enteritidis and S. Typhimurium, combined with the Salmonella-specific protein SseB, elicits robust and functional antibody responses to each of the components of the vaccine. Our data indicates that the application of MAPS technology to the development of vaccines targeting invasive forms of Salmonella is practical and merits additional consideration.

Keywords: Enteritidis; MAPS vaccine; OSP; Salmonella; SseB; Typhimurium; quadrivalent.

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Conflict of interest statement

F.Z., R.M. and Y.-J.L. are inventors of the MAPS technology which is now owned by GSK. F.Z., R.M. and Y.-J.L. are consultants to GSK.

Figures

Figure 1
Figure 1
Comparison of three fusion proteins in Salmonella Enteritidis MAPS. Pre: rabbit sera before MAPS immunization (closed symbols). P1: rabbit sera after one immunization (open symbols). P2: rabbit sera after two immunizations (half-filled symbols). (A) S. Enteritidis OSP IgG antibody titer from rabbits immunized with MAPS constructs to compare carrier function of each fusion protein. (B) Analysis of IgG antibody against IpaB, SseB, and CP1 from rabbits immunized with MAPS constructs. (C). Analysis of IgG antibody function generated by MAPS immunization. Opsonophagocytic assays using P1 and P2 sera were used to determine the killing titers for each rabbit. Data were collected from two or more experiments; a representation is shown here.
Figure 2
Figure 2
Role of SseB in bacterial killing during opsonophagocytic assays. (A) Analysis of the killing capability of SseB-immunized rabbit sera against S. Typhimurium (circles) and S. Enteritidis (squares). Pre: rabbit sera before MAPS immunization (closed symbols). SseB: sera from rabbits immunized with SseB protein alone (open symbols). (B) Protection comparison of SseB MAPS compared with CP1 MAPS against S. Typhimurium (circles) and S. Enteritidis (squares) in opsonophagocytic assays. Killing titers were divided by OSP antibody titers to normalize the killing activity per antibody. Data were collected from two or more experiments; a representation is shown here.
Figure 3
Figure 3
Analysis of S. Typhimurium MAPS immunogenicity. (A) Analysis of antibody production against S. Typhimurium OSP after two MAPS immunizations. Pre: rabbit sera before MAPS immunization (closed symbols). P1: rabbit sera after one immunization (open symbols). P2: rabbit sera after two immunizations (half-filled symbols). (B) Analysis of SseB antibody production after immunization with S. Typhimurium MAPS vaccines. Pre: rabbit sera before MAPS immunization (closed symbols). P1: rabbit sera after one immunization (open symbols). P2: rabbit sera after two immunizations (half-filled symbols). (C) Analysis of killing activity of immunized rabbit sera after two doses of S. Typhimurium MAPS vaccines. Depicted are the inverses of the sera dilutions in which a minimum of 50% of the bacteria were killed. The dotted line indicates the killing activity of rabbit sera prior to immunization. Data were collected from two or more experiments; a representation is shown here.
Figure 4
Figure 4
IgG antibody production by multivalent MAPS. (A) Analysis of OSP IgG antibody of Bivalent SseB S. Typhimurium and S. Enteritidis MAPS constructs. (B) Analysis of quadrivalent SseB MAPS antibody production against polysaccharide from four Salmonella serovars. (C) Analysis of SseB antibody production for bivalent and quadrivalent MAPS immunizations. Data were collected from two or more experiments; a representation is shown here. Pre: rabbit sera before MAPS immunization (closed symbols). P1: rabbit sera after one immunization (open symbols). P2: rabbit sera after two immunizations (half-filled symbols).
Figure 5
Figure 5
Antibody function analysis of multivalent MAPS constructs after two rabbit immunizations. The inverse of the sera dilution in which 50% of the bacteria were killed is shown. (A) Antibody functionality analysis of bivalent MAPS immunizations against S. Typhimurium and S. Enteritidis in opsonophagocytic assays. (B) Analysis of antibody killing activity against the four Salmonella serovars. Opsonophagocytic assays were used to analyze S. Typhimurium, S. Enteritidis, and S. Typhi. Bactericidal assays were used to analyze S. Paratyphi. Data were collected from two or more experiments; a representation is shown here.
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