title: Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model.
abstract: While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control-rats received saline; Adjuvant-rats received the adjuvant MPLA, and Vaccine-rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy.
authors.affiliation: Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT) - Barra do Garças, Mato Grosso State, Brazil.
authors.forename: Rafaianne Q
authors.initials: RQ
authors.lastname: Moraes-Souza
authors.affiliation: Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Gerais State, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Reinaque
authors.affiliation: Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT) - Barra do Garças, Mato Grosso State, Brazil.
authors.forename: Thaigra S
authors.initials: TS
authors.lastname: Soares
authors.affiliation: Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Gerais State, Brazil.
authors.forename: Ana Luiza T
authors.initials: AL
authors.lastname: Silva
authors.affiliation: Laboratory of Cell-Cell Interactions, Morphology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rodolfo C
authors.initials: RC
authors.lastname: Giunchetti
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Maria A S
authors.initials: MA
authors.lastname: Takano
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Milena A
authors.initials: MA
authors.lastname: Akamatsu
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Flávia S
authors.initials: FS
authors.lastname: Kubrusly
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Lúcio-Macarini
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Isaias
authors.initials: I
authors.lastname: Raw
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Iourtov
authors.affiliation: Division of Technological Development and Production (DDTP), Butantan Institute, São Paulo, Brazil.
authors.forename: Paulo Lee
authors.initials: PL
authors.lastname: Ho
authors.affiliation: Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Gerais State, Brazil.
authors.forename: Lilian L
authors.initials: LL
authors.lastname: Bueno
authors.affiliation: Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Gerais State, Brazil.
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Fujiwara
authors.affiliation: Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT) - Barra do Garças, Mato Grosso State, Brazil.
authors.forename: Gustavo T
authors.initials: GT
authors.lastname: Volpato
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D020964:Embryo Loss / Q000139:chemically induced*; D005260:Female; D005333:Fetus / Q000002:abnormalities* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007892:Leishmania braziliensis; D054332:Leishmaniasis Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology; D018811:Maternal Exposure / Q000009:adverse effects*; D008954:Models, Biological; D054464:Peroxiredoxins / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology; D011247:Pregnancy; D015800:Protozoan Proteins / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology; D051381:Rats
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D054464:Peroxiredoxins