IgA

The antibody response is crucial for preventing many viral infections and may also contribute to resolution of infection. When a vertebrate is infected with a virus, antibodies are produced against many epitopes on multiple virus proteins. A subset of these antibodies can block virus infection by a process that is called neutralization.

Antibodies can neutralize viral infectivity in a number of ways, as summarized in the illustration. They may interfere with virion binding to receptors, block uptake into cells, prevent uncoating of the genomes in endosomes, or cause aggregation of virus particles. Many enveloped viruses are lysed when antiviral antibodies and serum complement disrupt membranes.

Non-neutralizing antibodies are also produced after viral infection. Such antibodies bind specifically to virus particles, but do not neutralize infectivity. They may enhance infectivity because antibodies can interact with receptors on macrophages. The entire virus-antibody complex is brought into the cell by endocytosis. Viral replication can then proceed because the antibody does not block infectivity. This pathway may allow entry into cells which normally do not bear specific virus receptors.

Where in the body does antibody neutralization of viruses take place? Virions that infect mucosal surfaces encounter secretory IgA antibodies present at the apical surfaces of epithelial cells. Viruses that spread in the blood will be exposed to IgG and IgM antibodies. In fact, the type of antibody that is produced can influence the outcome of viral infection. Infection with poliovirus causes IgM and IgG responses in the blood, but mucosal IgA is vital for blocking infection. This antibody can neutralize poliovirus in the intestine, the site of primary infection. The live attenuated Sabin poliovirus vaccine is effective because it elicits a strong mucosal IgA response and provide intestinal immunity.  In contrast, the injected (Salk) polio vaccine does not produce intestinal immunity, and therefore is less effective at preventing spread of poliovirus in a population.

The vast majority of influenza vaccines are administered by injection and stimulate the production of IgG antibodies; they are poor inducers of mucosal IgA antibodies. The efficacy of influenza vaccines would likely be markedly improved if they could be designed to stimulate mucosal immunity. Flumist is a licensed, intranasally-administered infectious virus vaccine that has been shown to stimulate both mucosal and systemic immunity. Nine clinical trials have been conducted in children comparing the efficacy of Flumist with inactivated vaccine or placebo. An analysis of the results suggests that the intranasally administered vaccine is more effective in preventing influenza. These results underscore the role of local immunity in resistance to respiratory pathogens.

Rhorer, J., Ambrose, C., Dickinson, S., Hamilton, H., Oleka, N., Malinoski, F., & Wittes, J. (2009). Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials Vaccine, 27 (7), 1101-1110 DOI: 10.1016/j.vaccine.2008.11.093