Protective Immunity against Respiratory Syncytial Virus in Early Life after Murine Maternal or Neonatal Vaccination with the Recombinant G Fusion Protein BBG2Na

Abstract

Maternal and neonatal immunization were evaluated for their capacity to induce protective immunity against respiratory syncytial virus (RSV) lower respiratory tract infections in early life. Murine models were studied by use of a novel recombinant vaccine candidate, designated BBG2Na, which was derived in part from the RSV (Long) G protein. Maternal immunization resulted in the passive transfer of high levels of RSV-A antibodies to the offspring, which protected them from RSV challenge for up to 14 weeks. Indeed, protection correlated with the detection of RSV antibodies in the serum. Neonatal immunization with BBG2Na induced significant antibody responses even in the first week of life. Most importantly, these neonatal responses were not inhibited by the presence of RSV maternal antibodies. Consequently, the combination of maternal and neonatal immunization with BBG2Na resulted in the continual presence of protective levels of antibodies in the offspring.

CD4+T-Cell-Mediated Antiviral Protection of the Upper Respiratory Tract in BALB/c Mice following Parenteral Immunization with a Recombinant Respiratory Syncytial Virus G Protein Fragment

“…In addition, nasal Ab titers to BBG2Na in the offsprings were 2.3 Ϯ 0.6 and 1.9 Ϯ 0.57 log 10 , respectively (versus Ͻ0.3 log 10 in naive mice), which were also similar to the titers observed in BBG2Na-immunized mice (2.16 Ϯ 0.51 log 10 ). When challenged with RSV-A, lungs of all of these 2-and 4-week-old pups from BBG2Na-immuned mothers were protected, with virus absent or at the limit of detection of the assay in the LRT (1.74 Ϯ 0.38 log 10 TCID 50 /g of lung) (5). In contrast, they all demonstrated URT infection (Fig.…”

“…Therefore, we first asked whether the lack of URT protection following passive Ab transfer could be explained by the generation of lower serum BBG2Na IgG Ab titers following passive transfer than those observed following BBG2Na immunization. This hypothesis was assessed with a neonatal murine model in which transfer of maternal Ab from mother to pups is so efficient as to result in IgG Ab titers in pups similar to those in their immunized mothers (5). As previously demonstrated, serum BBG2Na Abs in the offspring of BALB/c mothers immunized twice with BBG2Na prior to mating reached means Ϯ standard deviation (SD) of 4.25 Ϯ 0.08 and 5.23 Ϯ 0.11 log 10 in 2-and 4-week-old litters, respectively (5).…”

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

“…The F protein has been shown to be most effective at inducing neutralizing antibodies and protective immunity in animal models (13, 14, 38, 52, 53, 58). The G protein also induces neutralizing antibodies and protective immunity (4,25,28,36,47,49,51), but it has features that contribute to RSV disease pathogenesis (5,12,29,41,54). One region in the RSV G protein contains a CX3C chemokine motif capable of binding to CX3CR1 and antagonizing the activities of CX3CL1 (56).…”

“…Evidence indicates that the RSV F protein is important in inducing protective immunity (19,38), but studies evaluating a BBG2Na vaccine candidate in combination with different adjuvants and by different routes of administration have shown a role for G protein in protection against RSV in rodents (4,10,17,32,43,44,49,51). The structural elements of the G protein fragment in the BBG2Na vaccine candidate implicated in protective efficacy were mapped, and five different B-cell epitopes were determined, i.e., residues 145 to 159, 164 to 176, 171 to 187, 172 to 187, and 190 to 204 (44,48).…”

Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis

“…In cotton rats, there is also evidence that high titres of antibody can interfere with vaccination against RSV in pups and adults 153,154 . In contrast, in murine studies, no detrimental effect of maternal antibodies was observed following RSV vaccination [155][156][157] and maternal antibodies may enhance the response in pups If this is ultimately shown to be true for GBS CPS-CRM197 conjugates then other protein carriers could be considered as alternatives.…”