Th2-Associated Local Reactions to the Acellular Diphtheria-Tetanus-Pertussis Vaccine in 4- to 6-Year-Old Children

Abstract

Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4-to 6-year-old children primed during infancy with DTaP (n ‫؍‬ 30) or DTwP (n ‫؍‬ 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (>50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically "high Th2 responders" as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.Morbidity and mortality to infectious diseases are maximal during early infancy, and as a consequence, the pressure to develop an increasingly broad range of vaccines in progressively younger age groups is increasing. An archetypal example is the diphtheria-tetanus-pertussis (DTP) vaccine, which provides protection against pathogens responsible for severe illness and death in millions of children worldwide, and initiatives to introduce versions of this and other vaccines for use in neonates to provide protection during the crucial first months of life are well advanced in many centers (3,11,17,29).The primary consideration underpinning research and development in this area continues to be that of safety, and the first major shift in formulation of the DTP vaccine from the original combination of whole-cell pertussis combined with tetanus and diphtheria toxoids (DTwP) to the new-generation acellular version (DTaP) was driven precisely by this imperative. Notably, the occurrence of febrile reactions in a small proportion of DTwPvaccinated children (6,8,13) which are likely to be associated with cell-mediated responses to the vaccine has provided the imp...

Sex differences in injection site reactions with human vaccines

“…These authors contend that the discrepancy between ultrasound and MRI/CT scan generated data reflects greater accuracy of the latter in measuring and showing the distinction between muscle and fat layers and lack of compression of the site being screened with MRI/ CT scanning compared with ultrasonography. Also of interest in this context is the observation by Scheifele et al 116 that in children aged 4-6 years the risk of large local reaction was significantly higher in children with a body mass index above the median value, suggesting that "the vaccine may not have been reliably injected into muscle in larger children. "…”

“…These reactions with acellular pertussis booster vaccination are associated with T helper 2 (Th2) cytokine production 115 due to a Th2 polarized cellular memory to DTaP. 116 Other explanations for the sex-difference in ISRs include injection route and hormonal status.…”

Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection

“…Although protection can be conferred by vaccination with whole-cell pertussis (wP) vaccines or modern acellular pertussis (aP) vaccines, a concern with wP and to a lesser extent aP vaccines is their reactogenicity after multiple booster doses (Barlow et al, 2001). Systemic and local side effects, such as febrile seizures, swelling and redness around the site of injection, and encephalopathy, although rare, have been reported (Rennels et al, 2000;Gold et al, 2003;Rowe et al, 2005).…”

Discontinuation of BCG Vaccination Precedes Significant Drop in Type 2 Diabetes in Japanese Children. Role of Inflammation and Cortisol Activity as a Cause of Type 2 Diabetes

“…Vaccines have been shown to cause cortisol release [23][24][25][26][27][28][29][30]. This can be explained because vaccines cause the release of IL-6 [31][32][33] an cytokine that causes cortisol release [34][35][36]. Japanese have increased cortisol secretion following immunization compared to Whites [37] and this explains why Japanese have higher rates of type 2 diabetes but lower rates of type 1 diabetes than Whites [4,11,38,39].…”