Serum and mucosal immunologic responses in children following the administration of a new inactivated intranasal anti‐influenza vaccine*

Abstract

Children are at considerable risk for influenza infection and may constitute the main vector for transmitting the virus to adults in the community. At present, the use of available vaccines in children is limited mainly because of a fear of side effects from the injection. Intranasal immunization was assessed as a painless, side effect-free method of facilitating the enrollment of children in vaccination programs. One intranasal dose of a trivalent inactive whole virus vaccine containing 20 microg of the three recommended seasonal viral strains was administered to 28 children recruited over two separate winter periods (1997/1998 and 1998/1999). No adverse effects were recorded. Serum IgG responses were determined by the hemagglutination inhibition (HI) method and nasal IgA responses by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%-94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1 strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999, respectively. The increase in GMT, as well as fourfold increases in titer level, was higher when calculated among the nonimmune children prior to vaccination. Of these, 50%-87.5% became immune following immunization. Local antibody response to the three viral strains was detected in 50%-55% of the immunized children. Also, 83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively. This mucosal response may forestall influenza development in its early stages, thereby contributing significantly to the reduction of influenza spread in the community.

Demonstration ofd-Octaarginine-Linked Polymers as Promising Adjuvants for Mucosal Vaccination through Influenza Virus Challenge

“…Immunoglobulin A (IgA) is secreted on the mucosa of the respiratory tract when mucosal immunity is acquired through natural infection of influenza viruses. Not only does secreted IgA block mucosal invasion of influenza viruses, but also the antibody is cross-protective against heterologous virus infection. − Mucosal vaccination is one of the most effective ways to reduce the risk of pandemics which result from incorrect prediction of epidemic strains or virus mutation. − FluMist was initially launched as a mucosal vaccine which included cold-adapted influenza viral strains selected on the basis of WHO prediction. − The vaccine-induced mucosal IgA and cell-mediated immunities protect hosts from infection with antigenically matched and distant viral strains. FluMist, however, is not indicated for high-risk groups such as infants and the elderly, presumably due to the potential jeopardy of live attenuated vaccines.…”

Mechanisms of Broad Cross-Protection Provided by Influenza Virus Infection and Their Application to Vaccines

“…The calculation that would allow extrapolation from mice to humans to determine the appropriate vaccine dosage was also confirmed by the use of another experimental model. Thus, the results of clinical trials, in which whole inactivated virus particles alone were administered intranasally and resulted in the enhanced production of both local HA-specific IgA Abs and serum HI Abs (65)(66)(67)(68)(69), were also roughly repeated in BALB/c mice immunized intranasally with 0.1 μg whole inactivated virus particles without adjuvant (0.1 μg/mouse) (unpublished data). The high immunogenicity of the inactivated whole-virion vaccine, which is almost equivalent to that of the adjuvant-combined split-product vaccine, could be explained by the adjuvant action of single-stranded RNAs via TLR7 (17)(18)(19)71).…”

“…Concentrated split-product vaccines (i.e., threefold concentrated vaccines), which are administered intranasally as an aerosol, are effective at inducing local HA-specific IgA Abs and at preventing infection by the live virus, according to results of human trials (64). Whole inactivated virus particles are also administered intranasally and result in an enhanced production of both local HA-specific IgA Abs and serum HI Abs in clinical trials (65)(66)(67)(68)(69). In addition, intranasal immunization with formalin-inactivated whole viruses, but not ether-split vaccines, induces a broad spectrum of heterosubtypic protective immunity in mice (70).…”

Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities

“…[15][16][17] Mucosal vaccination is one of the most effective and adaptive immunization strategies for protecting hosts against infectious pathogens that invade epithelial cells on the mucosa such as influenza viruses. [18][19][20][21][22] Both humoral responses: immunoglobulin G (IgG) and immunoglobulin A (IgA), are observed in the blood and on the mucosa, respectively, in hosts immunized mucosally with antigens. IgA secreted on the mucosa, which is not induced through conventional parenteral vaccines, possesses a couple of unique immunological properties.…”