Optimal Use of Vaccines for Control of Influenza A Virus in Swine

Abstract

Influenza A virus in swine (IAV-S) is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health.

Keywords: immune response; influenza A virus in swine; surveillance; vaccines; veterinary diagnostics.

Figure 1

Influenza virus infection cycle. Basic structural features of an influenza virus are diagrammed in the top left corner. Infection begins with the binding of hemagglutinin (HA) proteins to receptor molecules on the cell surface. The cycle is completed when new particles, each containing eight RNA segments, bud off from the cell membrane. Neuraminidase (NA) protein cleaves the bonds between HA and sialic acid molecules, allowing new virus to disperse. Boxes labeled A–D indicate points in the cycle that may be inhibited by antibodies or T cells. (Figure used with permission from the New England Journal of Medicine, Linda C. Lambert and Anthony S. Fauci, Influenza Vaccines for the Future, Vol. 363:2039. © 2010 Massachusetts Medical Society).

Figure 2

Antigenic shift. There are two ways that an influenza virus with new antigenic properties may enter the pig population. (A) Virus that was previously adapted to another animal host, such as avian species, enters pigs and adapts to circulate efficiently in swine. The diagram portrays the inter-species transmission of an avian H1N1 virus, which became established in European swine populations; (B) Virus previously adapted to another host, such as birds or humans, co-infects a pig along with a common swine-adapted strain. This can lead to gene reassortment, producing a new “reassortant” virus that contains an HA and/or NA antigenically different from those that previously circulated in swine. The diagram portrays reassortment between human seasonal H1N1 and swine H3N2 viruses. In both (A) and (B), the swine population lacks antibodies to important surface proteins of the new virus.

Figure 3

Antigenic drift. Over time, random mutations in HA and NA genes of an influenza A virus in swine (IAV-S) strain may cause significant changes in antigenic properties. A swine herd with population immunity to IAV-S has neutralizing antibodies specific to a strain that was previously encountered through infection or vaccination. However, if antigenic drift produces a new variant strain that pre-existing antibodies in the herd are unable to neutralize, the pigs become susceptible to reinfection.

Figure 4

Decision tree for selection of IAV-S vaccine strategy to control a specific herd isolate. Due to the diversity and rapid evolution of IAV-S, there are currently no one-size-fits-all vaccine options. Since commercial polyvalent vaccines from different manufacturers contain different strains, diagnostic data (HA sequence and/or serological comparisons) may identify one vaccine that matches a specific field strain better than others. In some cases, data may indicate that commercial polyvalent vaccines offer no close matches to the field strain, suggesting a greater advantage for custom vaccines.