The level of circulating serum antibodies in each of the 4 infant baboons and 3 age-matched unvaccinated baboons was decided for pertussis vaccine antigens by enzyme-linked immunosorbent assay (Figure ?(Physique11strain D420, divided between the trachea and nasal cavity
The level of circulating serum antibodies in each of the 4 infant baboons and 3 age-matched unvaccinated baboons was decided for pertussis vaccine antigens by enzyme-linked immunosorbent assay (Figure ?(Physique11strain D420, divided between the trachea and nasal cavity. substantial leukocytosis ( 50 000 white blood cells/L) is associated with increased mortality rates [10]. It is postulated that this high leukocyte mass can trigger thrombi formation, restrict blood flow, and exacerbate the development of pulmonary hypertension [11]. Several strategies have been proposed to reduce the incidence of pertussis in infants during the first few months of life. These include adolescent pertussis booster vaccination, cocooning, neonatal vaccination, and maternal vaccination. A marked increase in pertussis incidence in 11C18-year-old individuals at the beginning of the 21st century led to the introduction of a tetanus, reduced-dose diphtheria, reduced-dose acellular pertussis (Tdap) adolescent booster vaccine 1-Methyladenosine in the United States. It was postulated that this vaccination strategy would reduce the circulation of in the population and thereby reduce infant exposure. However, although Tdap successfully decreased pertussis incidence among recipients aged 11C18 years, there was no impact on disease incidence among infants [12]. Similarly, cocooning was proposed as a mechanism to reduce infant exposure to by vaccinating parents and siblings of newborns, as well as other frequent contacts. The rationale for cocooning is based on the evidence that infants most often acquire pertussis from a parent or other family member [13C15]. However, in an evaluation of the effectiveness of cocooning in 4 Houston hospitals, no significant benefit was observed [16]. Also, while cocooning programs have achieved moderate vaccination coverage among postpartum mothers, there has been limited success in vaccinating fathers or other family 1-Methyladenosine members, leading to the conclusion that this approach would be difficult to implement [17, 18]. Additionally, we recently showed that baboons vaccinated with DTaP (a diphtheria, tetanus and acellular pertussis vaccine formulation in which higher doses of each antigen are present) are not protected from contamination and can transmit pertussis to naive cage mates, suggesting that cocooning, even if fully implemented, may not optimally protect infants [19]. The apparent failures to reduce infant pertussis by vaccinating contacts likely suggest that newborns need antiCantibodies, to be guarded for the first few months of life. Immunization at birth (ie, neonatal vaccination) has been proposed, based on the demonstration that newborns are able to mount antibody responses to acellular pertussis vaccination [20, 21]. Alternatively, vaccinating women in the third trimester of pregnancy has been proposed and is now recommended by the US Advisory Committee on Immunization Practices (ACIP) [22, 23]. Several studies demonstrated efficient transplacental transfer of antiCantibodies, supporting the potential of this approach [24C26]. While both neonatal and maternal vaccination strategies induce elevated antiCantibody titers in newborns, the lack of a serological correlate of protection presents a significant challenge in demonstrating 1-Methyladenosine the clinical efficacy of either approach. We developed a baboon model of pertussis that accurately reproduces severe clinical pertussis, including heavy respiratory colonization, leukocytosis, prolonged cough illness, and transmission from infected to naive animals [27C29]. In addition to providing an excellent model of pertussis, the baboon has proven to be a relevant model for reproductive studies, since their reproductive cycles are year round, and they form a single discoid placentation that is very similar to that in humans [30, 31]. In addition, it has been documented that baboons possess the same 4 immunoglobulin G (IgG) subclasses as humans [32], and that transplacental transfer of IgG from mother to fetus occurs as in humans [33, 34]. These considerations support the use of the baboon model of pertussis vaccination and contamination for studying the effectiveness of neonatal and maternal vaccination. This model provides a unique opportunity to determine if maternal and/or neonatal vaccination confers protection to very young infant primates. Newborn baboons vaccinated at 2 days of age or at 2 days and 28 days of age with licensed DTaP vaccines were guarded from a robust challenge at 5C6 weeks of age. Protection was also observed in 5C6-week-old animals born Rabbit Polyclonal to SFRP2 to DTaP-primed mothers that were boosted at the beginning of their third trimester. These results demonstrate that neonatal vaccination and maternal vaccination confer protection in the baboon model and, for the first time, provide proof of concept for 1-Methyladenosine these strategies in 1-Methyladenosine a primate model. MATERIALS AND METHODS.