Impact of Influenza Vaccine Formulation with a Detailed Analysis of the Cytokine Response

Abstract

Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme‐linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN‐γ (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response.

Kinetics of Immune Responses to Influenza Virus-Like Particles and Dose-Dependence of Protection with a Single Vaccination

“…3D). The delayed induction of IgG1 antibodies was similar to that observed in mice intramuscularly immunized with a single dose of 15 g of split influenza vaccine (11,30). The addition of either mLT(R192G) or CTB significantly increased the levels of IgG2a by fourfold ( Fig.…”

“…Studies of influenza VLPs as a vaccine candidate are still in an early developmental stage, and there is no detailed study of the kinetics of inducing virus-specific immune responses and protective efficacy after intranasal immunization with a single dose or two doses of influenza VLPs. Although limited previous studies demonstrated immune responses after one or two systemic vaccinations with inactivated whole virus or split vaccines (11,12,30), the HA dose-sparing effects on the kinetics of immune responses including isotypes of antibodies, functional antibodies, and protective efficacy, including lung viral titers and inflammation after lethal infection, remain largely unknown after mucosal vaccination. VLPs containing influenza M1 alone did not induce protective immune responses (25).…”

History of infections and vaccinations and risk of lymphoid neoplasms: does influenza immunization reduce the risk?

“…This result is pertinent to the recent emphasis on the prognostic relevance of leukocytosis in both PV and ET. 7 Our findings also underline the potential confounding effect of sample accrual time on result interpretation. Finally, we underscore the fact that the current study utilized DNA from archived bone marrow and should not be compared with other studies that have used either DNA 2 Several studies have shown that selected aspects of a history of infection and vaccination may be related to the risk of LN.…”

“…Depending on the formulation, whole or split inactivated influenza vaccine produces an immune response towards Th1 type of cytokines (IL-2 and IFN-g) or Th2 type of cytokines (IL-4, IL-10) respectively. 7 Repeated vaccinations could imbalance in the regulation and expression of Th1 and Th2 cytokines towards a Th1 thought to be protective against cancer. A shift in the balance of the Th1/Th2 response may play a role in aetiology of LNs as suggested by Holly et al 8 This hypothesis is also supported by recent findings that genetic variation in two key genes of Th2 pathway (IL-10, IL-4) could be associated with NHL.…”

Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling

“…Whereas whole-virion vaccines are more immunogenic than other formulations (e.g., split and subunit vaccines) in humans and mice (7,(75)(76)(77)(78), they have been replaced by splitvirion types because of the high incidence of adverse effects such as febrile illness and local reactions at the injection site (79)(80)(81)(82). It is generally accepted that inflammatory cytokines produced from innate immune cells (i.e., DCs) are the primary cause of adverse effects in subjects vaccinated with whole-virion vaccines (75,83). Therefore, it is conceivable that a vaccine strategy selectively targeting B cell-intrinsic TLR signaling at the memory stage could reduce adverse effects while keeping the capacity for prompt recall response fairly intact.…”