High Titers of Circulating Maternal Antibodies Suppress Effector and Memory B-Cell Responses Induced by an Attenuated Rotavirus Priming and Rotavirus-Like Particle-Immunostimulating Complex Boosting Vaccine Regimen

Abstract

Vaccination of neonates faces many challenges due to the immaturity of the neonatal immune system and interference by maternal antibodies (MatAbs) present at vaccination. Various degrees of interference of vaccine-induced immune responses by MatAbs have been reported for live vaccines such as measles and Sabin oral poliomyelitis vaccines as well as for nonreplicating vaccines (i.e., inactivated or subunit vaccines) such as tetanus, diphtheria, Haemophilus influenzae, hepatitis A and B, classical swine fever virus, and measles virus vaccines (5,6,10,12,16,34). The effects of MatAbs on DNA vaccines are variable. Mice immunized with a DNA vaccine coding for hepatitis B envelope protein S (HBs) in the presence of maternally derived HBs antibodies had lower antibody responses than those immunized with the vaccine in the absence of HBs antibodies, suggesting that MatAb interference also occurs for DNA vaccines (34). In contrast, a DNA vaccine coding for gB and gD of pseudorabies virus primed immune responses in the presence of MatAbs more efficiently than a conventional vaccine or in the absence of MatAbs (naïve pigs) (31). The effects of MatAb, whether positive (enhancing) or negative (suppressive), may depend on the ratio between the amount of MatAb and the antigen present (26,28). Optimal amounts of MatAb can enhance B-cell responses by forming antigen-antibody complexes that induce complement deposition, in turn engaging the B-cell receptor and the complement receptor CD21, thereby producing costimulation of B cells via CD19/CD81. On the other hand, MatAbs can neutralize live vaccines and reduce the antigen mass available for immune response induction. The positive or negative influences of MatAbs cannot be reliably predicted; experimental models and field trials are required to study the MatAb effects on vaccines.Rotavirus infections can occur in infants under 3 months of age, even when the levels of MatAb in the circulation (acquired from placental transfer) and intestine (acquired from breast milk) remain high. It has been suggested that the variable efficacies and seroconversion rates in many rotavirus vaccine trials in human infants may be associated with these preexisting antibodies (likely maternally derived in children less than 6 months of age) (22). However, controlled studies to define the influence of MatAbs on rotavirus vaccines are lacking. Using gnotobiotic pigs, Hodgins et al. (9) previously demonstrated that induction of antibody-secreting cell (ASC) responses after virulent Wa human rotavirus (HRV) (VirHRV) primary infection and challenge was suppressed in the

Activation of the RIG-I Pathway during Influenza Vaccination Enhances the Germinal Center Reaction, Promotes T Follicular Helper Cell Induction, and Provides a Dose-Sparing Effect and Protective Immunity

“…2A). However, this may have been due to the inhibitory effect of high levels of circulating antibodies, after the single immunization, on the booster effect in the 5-g HA-immunized mice, since such a negative-feedback inhibitory effect of antibodies has been noted previously (28). We further compared the dose-sparing efficacy of RIG-I pathway activation with TLR4, TLR7, and alum (NLR) pathway activation in inducing recall memory antibody responses when a sparing dose of 0.5-g HA vaccine was used.…”

Immunogenicity of an AutogenousStreptococcus suisBacterin in Preparturient Sows and Their Piglets in Relation to Protection after Weaning

“…Since this study did not include colostrum-deprived piglets, this question remains open. It is noteworthy that other studies have observed a good immune response in suckling piglets with vaccines against other pathogens and have demonstrated that maternal antibodies reduced the impact of vaccination in swine (17).…”

“…The protective efficacies of the different S. suis vaccination regimes are unknown, since comparative evaluations have not been described. Maternal antibodies might exhibit positive or negative effects of various degrees on vaccine-induced immune responses in progeny, as has been shown for different pathogens (17,18). The working hypothesis of this study was that S. suis immunization of preparturient sows might elicit protective passive maternal immunity but might also influence active immunization of piglets.…”

Strategies for Design and Application of Enteric Viral Vaccines

“…The blocking effects of maternal antibodies have been demonstrated for both enteric and respiratory vaccines, such as RV (37)(38)(39), swine influenza (40,41), bovine respiratory syncytial virus (42), and bovine viral diarrhea virus (43)(44)(45). These studies have suggested that for live vaccines, the presence of maternal antibodies may result in low rates of seroconversion.…”