Total viral genome copies and virus–Ig complexes after infection with influenza virus in the nasal secretions of immunized mice

Abstract

The kinetics of infectious virus (p.f.u.), total virus and virus-Ig complex formation following influenza A/PR8 (H1N1) viral infection was examined in the nasal secretions of naive mice and mice immunized with A/PR8, A/Yamagata (H1N1), A/Guizhou (H3N2) and B/Ibaraki influenza viruses. The total number of virus particles and the number within virus-Ig complexes, captured in advance using an anti-mouse Ig-coated plate, were determined on the basis of viral genome copy number using quantitative RT-PCR. The kinetics of infectious and total virus particle formation, the latter of which increased by 10 3-10 4-fold above infectious virus numbers, showed that virus elimination from the nasal area was earlier in A/PR8, A/Yamagata and A/Guizhou-X virus-immunized mice, in decreasing order, compared with naive mice. Early virus elimination correlated with the level of A/PR8 virus-reactive antibodies in immunized mice. Virus elimination coincided with the appearance of virus-Ig complexes shortly after infection. This result suggested that antibodies led to the formation of immune complexes in a dose-dependent manner together with a reduction in number of infectious virus particles. The fact that a large number of virus particles was observed in immune complexes for a wide range antibody levels made it difficult to detect slight differences in virus number within the immune complexes, depending on antibody level. These results suggested that the formation of virus-Ig complexes in virus-immunized mice shortly after infection is involved in early virus elimination, which is determined by the strength of protective immunity against challenge viruses.

Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice

“…Therefore, in the upper respiratory tract damage to the epithelial layer during viral replication may be important for passage of IgG across the mucosal barrier [48]. Yoshikawa et al [37] have in an elegant study demonstrated that viral neutralization by IgG antibodies alters the kinetics of influenza infection. We have shown here that high concentrations of vaccine-induced influenzaspecific serum IgG were important in significantly reducing viral shedding but did not completely prevent infection.…”

“…This contrasts with the earlier and transient detection of IgG and IgA ASC in the lungs found in this study upon viral challenge of vaccinated mice. In mice, influenza infection elicits immunological memory which upon subsequent viral encounter results in an earlier increase in the number of ASC and a concomitant increase in antibody production leading to reduced viral shedding from 2 to 3 days after infection [36,37]. Further studies are needed to evaluate the role of the ASC response in the NALT to provide a clearer picture of the B-cell response in the upper respiratory tract after viral challenge of parenterally vaccinated mice.…”

“…Nonspecific inhibitors were removed by treating the serum overnight at 37 C with receptor destroying enzyme (Denka Seiken, Tokyo, Japan) and then subsequent inactivation at 56 C [25]. The assay was carried out using 8 haemagglutinating units of virus and 0.7% turkey red blood cells as previously described [24].…”

A lack of antibody formation against inactivated influenza virus after aerosol vaccination in presence or absence of adjuvantia

“…In the case of AIV, aerosol vaccination using live virus is not desirable because of its zoonotic potential and because of the risk for virus reassortment. Mucosal vaccination via the respiratory route has several advantages: it induces both local and systemic immune responses (Atmar et al, 2007;Tseng et al, 2009;Worrall et al, 2009), it could halt infection already at portal of entry (Yoshikawa et al, 2004) and it is suitable for mass application.…”

Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

“…DTH-mediating Th1 cells are also generated from naä ƒve CD4 ＋ T cells and are involved in blocking viral replication in the mucosal tissue; however, Th1 cell induction following live virus infection is weaker than that induced by administration of inactivated virus (9,16 However, a recall response triggered with a variant virus, known as``original antigenic sin,'' is seen upon infection with a novel influenza strain: Abs against the original virus strain are produced, while Abs against the novel strain are not produced, resulting in exacerbation of the severity of influenza illness (21). Original antigenic sin may be more profound in a host sequentially infected with live viruses than in a host sequentially immunized with inactivated vaccines (13,(22)(23)(24)(25). Giving increased doses of challenge antigen and using antigen together with an appropriate adjuvant can overcome the reduction in Ab response and alleviate original antigenic sin responses to influenza viruses.…”