Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

Abstract

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

Immunization of preterm infants: current evidence and future strategies to individualized approaches

“…After a booster dose, 81.7% of a preterm group aged less than 28 weeks achieved protective antibody levels. Similarly, protective antibody responses were observed against tetanus and diphtheria in preterm infants, while lower antibody levels were found for Hib and HepB [ 29 ]. In this study, however, preterm infants had a diminished immunological memory to pertussis.…”

“…In order to improve immunization strategies for the specific situation of preterm infants, it is important to have a comprehensive understanding of the distinct neonatal features of immunity. There are major immunological differences between preterm and term infants with relevance to vaccine responses, for example: (i) reduced amounts of protective maternal antibodies, (ii) reduced barrier function of skin and mucosa (iii) immature innate immune function (leukocyte migration ↓, complement function↓, numbers of dendritic cells and monocytes↓, diminished antigen presentation by high adenosine levels), (iv) predominance of transitional B cells with reduced antibody affinity and maturation, (v) distinct cytokine profiles of T cells upon Toll-like receptor stimulation (Interferon-γ↓, IL-10↑) and (vi) reduced proliferation of T cell effector and memory cells [ 3 , 29 ]. Preterm infants primarily rely on innate immune processes and barrier protection for their defense against pathogens.…”

“…•WHO: birth dose can be given to LBWI and PIs but should not count as part of the primary 3-dose series •rare AE: non-suppurative lymphadenopathy [24] •limited data on ELGANs RCTs: [24,25,27] •reduces risk of TB by up to 83% and induces protection for 10 years [28] •overall immunogenicity of > 95% (PI > 31 weeks) [20,29] •reduces mortality in high-risk regions [30,31] RCTs: [24,32,33 •CRI as a non-specific self-limiting stress reaction especially in most vulnerable infants [14,[34][35][36][37] but no difference in CRI-rates in RCT between DTaP exposed and unexposed PIs [38][39][40] •post-immunization fever: 1.4%-33% [13,[41][42][43] RCTs: [38,44] •excellent immunogenicity of most hexavalent components across all GA-and BW-groups [14,45] •inconclusive reports for pertussis and Hib vaccines [45][46][47][48] •Lower response of PIs to certain polio serotypes [14,[49][50][51], Hib [52][53][54] and HBV [15-17, 19, 55] no RCTs •safe and well tolerated by PI [56,57] •compar...…”

“…Moreover, cell-mediated recall responses of preterm infant leukocytes to short hepatitis B exposure were reduced as compared to term infants and dependent on pre-existing antibody levels. Gestational and chronological age might be key factors of reduced immunogenicity to some vaccines, e.g., HepB, or vaccine components [30], and preterm infants may require an extra dose or early booster vaccination [28,29].…”

A retrospective study of hepatitis B vaccination in preterm birth and low birth weight infants born to hepatitis B surface antigen-positive mothers: Time to close the policy-practice gap

“…Existing studies have investigated the immunogenicity of HepB in PTB and LBW infants, while these results were not conclusive and varied widely among studies. 7–10 Therefore, the immunization strategy of HepB for PTB and LBW children varies among countries.…”