This wiki brings together the information gathered by CDPQ swine health and biosecurity team as part of a project carried out for Quebec pork industry. The main objective of this project was to analyze the possible actions at the provincial level (sequences and vaccines) to better control the effects of swine influenza on the pig population.

This project is the first step of a more global swine health management work plan for endemic diseases defined by the Quebec swine health advisory board (CMEP) from «Équipe québécoise de la santé porcine (EQSP)». The Quebec endemic disease swine health management plan for 2020-2025 is available online (in French).

The work team of this project carried out a review of the main concepts necessary for the implementation of structuring actions to better control influenza virus consequences at the provincial level. The main activities carried out were:

* A summary of the structure of the influenza virus (see section Influenza virus).

• A summary of the main actions making it possible to control the disease at the farm level (see the Prevention and control on the farm section).
• A consultation of experts and stakeholders in the management of issues related with the circulation of the influenza virus in the pig population. More specifically, experts from various laboratories and experts involved in the development and sale of commercial and autogenous vaccines. (see the list of consulted expert-partners).
• A picture of the influenza virus strains that circulate at the provincial level (see the Portrait des virus (Québec, Canada) section).
• A comparison of the strains present in the main Canadian regions (QC, ON vs WEST) to better understand the similarity or the diversity of the strains in Canada (see section Portrait des virus (Québec, Canada)).
• A list of actions that could be rolled out at the provincial or Canadian level to obtain better control of the swine flu virus.

All of the Quebec laboratories that participated in this study (MAPAQ, FMV, Biovet and Demeter) propose similar services to their veterinary clients to detect the presence of the influenza virus and to characterize the viruses. The presence of the virus is mainly established by nucleic acid amplification tests PCR of a gene specific to type A influenza present in the samples obtained from pigs (eg: oral fluids). After confirmation of the presence of the virus, it can be characterized by identifying the subtype (H and N), by sequencing the hemagglutinin (HA) protein gene or by sequencing the whole virus (see section Diagnostic et caractérisation du virus.

The picture of the circulating influenza viruses in Quebec is currently produced every three months by MAPAQ. The classification used by MAPAQ laboratories is limited to the subtypes (H|N) of type A viruses. It is important to underline that the MAPAQ laboratory offers a free service to characterize the influenza virus subtypes circulating in Quebec pig population. For more details, see Portrait des virus influenza (Options). The work carried out by the MAPAQ laboratory shows that the following viruses are present in the pig population of Quebec: H1N1 and H3N2 are frequent; Pandemic H1N1 and H2N1 are occasionally observed; H3N1 is almost never identified. For more details, see “Portrait des virus influenza au Québec (sous-types H|N)”.

In recent years, there have been several initiatives making it now possible to improve the classification of porcine influenza viruses by sequencing the HA gene (≈ 1700 bases). This methodology is prioritized by all the experts who work with the idea of ​​developing commercial and autogenous vaccines better suited to the viruses circulating in pig populations. The proposed techniques classify the subtypes (H1) and the subtypes (H3). For more details, see “Portrait de la circulation des virus influenza (clades H|N)”.

The synthesis of the analyzes of the HA gene sequences available in the databases of three laboratories in Quebec (Biovet, Demeter and FMV) and those available at the “Laboratoire national de microbiologie de Winnipeg” show that the distribution of swine influenza viruses in Quebec ( 2018-2020), in the North American classification system is quite different from the viruses found in Ontario and Western Canada (MB). For more details, see: Portrait of the circulation of influenza viruses (H | N clades). It will be noted that the dominant clade of H1 viruses in Quebec is the “β” clade and that it has almost no H1 virus of the “α” clade. The available data suggest the opposite situation in Manitoba (dominance of the “α” clade and absence of the “β” clade). Finally, the available data suggest the presence of these two clades (α and β) in Ontario. This observation is not so surprising, because there is generally little transport of pigs from the west of the country to Quebec.

Vaccination for influenza is a technique of prevention and control of influenza recognized by all professionals of human health and various animal species. Scientific work and field observations all show the importance of homology between the strain (s) of virus integrated in the vaccine and those circulating in the target population.

Canadian pork producers have access to some commercial vaccines and they also have the option of developing autogenous vaccines in accordance with Canadian Food Inspection Agency guidelines (ACIA).

Several veterinarians and pork producers in Quebec are interested in the development and rollout of autogenous vaccines that more specifically target strains circulating in Quebec farms because commercial vaccines are often ineffective because they do not contain the right strains.

CDPQ team review suggests that there are two working options for the development of autogenous vaccines:

1. Isolation, cultivation of the target viruses and manufacture of an inactivated and adjuvanted virus vaccine (Gallant Laboratories technology)
2. Synthesis of RNA particles homologous to the H gene of the targeted viruses and manufacture of a vaccine (Sequivity technology from Merck).

Quebec production systems veterinarians have already developed autogenous vaccines for animals in their production systems with these two technologies. Sequivity (Merck) technology is newer and is attracting a lot of interest because it does not require cultivation of the virus.

Discussions and consultations with technical staff from the three Quebec laboratories (Biovet, Demeter and FMV) who have the expertise to analyze and interpret HA sequence data showed that the methodologies were based on similar biological concepts, but that working procedures were different between institutions and experts. Three principles are used to compare and identify strains that might be good candidates for making an autogenous vaccine:

1. Clade method (all experts)
2. Epitope method, a concept that integrates several antigenic sites (Demeter)
3. Method of certain targeted antigenic sites (FMV and Biovet)

Despite the diversity of methodologies, the synthesis of the work carried out by the three laboratories shows that they all come to a similar conclusion (see the three reports). A few virus strains (6 to 10) should be sufficient cover a significant proportion of the strains in circulation in Quebec pig population . This concept can be visualized in the three-dimensional representations produced by Dr. Robert Charette (with permission).

• A three-dimensional projection of the epitope distance matrix (H1_QC) (see here)
• A three-dimensional projection of the epitope distance matrix (H3_QC) (see here)

The information gathered during this project is in favour of the concept of regional vaccine development. This idea is promising, but this concept should be validated by pilot projects.

Quebec veterinarians and pork producers have a great interest in the development and rollout of regional vaccines. Conceptually, the activities required for the development and roll-out of an autogenous vaccine on a farm or production system are quite similar to those required for the development and rollout of a regionnal vaccine. (Selection of strains and manufacture of a vaccine). In either case, the stakeholders and partners will have to follow CFIA guidelines.

As the time of this writing (fall 2020), swine health professionals have to understand that the CFIA is proposing clear guidelines for the development of autogenous vaccines that will be used on the farm, but does not propose official guidance for the development of regional vaccines. The CFIA team has authorized a pilot project in Ontario View announcements.

Five structuring actions were selected and are recommended by CDPQ swine health and biosecurity team.

1. Implement incentive programs to increase sequencing and characterization of influenza viruses (H1 and H3).
2. Develop a concept of sequence sharing to have a complete and detailed inventory of the diversity of strains in circulation in Quebec.
3. Promote the development of commercial vaccines and regional autogenous vaccines adapted to virus strains circulating in Quebec.
4. Promote a clarification of the regulatory framework of the Canadian Food Inspection Agency (CFIA) for the development and rollout of regional vaccines.
5. Carry out a pilot project to develop the expertise to rollout regional vaccine.