Today we are sharing a recent publication from the Torremorell lab regarding the impact of vaccination on the diversity of influenza variants in pigs.
The full article is available on the Veterinary Microbiology website.
Methods
- Samples from a previous study (published paper available) were analyzed for this study
- Nasal swabs from the following groups were used:
- COM/COM, AUT/AUT, AUT/COM, COM/AUT, LAIV/COM, combined into the PRIME BOOST group
- LAIV/NONE also called SINGLE LAIV
- NO VAC/CHA also called NO VAC
- Where COM=commercial vaccine, AUT=autogenous vaccine, LAIV=Live Attenuated Influenza A vaccine, NO VAC=no vaccine, CHA=Challenged
- PRIME BOOST, SINGLE LAIV and NO VAC pigs are characterized as contact pigs
- 2 samples from each of the seeder pigs as well as the inocula were analyzed as well
- Samples were tested by PCR and sent for next generation sequencing if Ct<35 and tested by a multiplex PCR to detect co-infections
Results
- PRIME BOOST pigs had significantly higher average HI titers against both challenge viruses compared to SINGLE LAIV and NO VAC pigs.
- A higher number of H1-specific IFN-γ cell counts was observed in NO VAC pigs
- 43% of the seeder pigs had proof of co-infection (with the subtype other than the one they were inoculated with) and some shed that other subtype
- PRIME BOOST pigs generally shed fewer viruses for both H1N1 and H3N2
- 4 out of 80 PRIME BOOST pigs had co-infections compared to 5 out of 10 SINGLE LAIV pigs and 4 out of 10 NO VAC pigs
- The highest genetic distance (within each contact group) was found in the sequences from the SINGLE LAIV pigs for both H1N1 and H3N2 subtypes.
- More single nucleotide variation (SNV) was found amongst the H1N1 sequences compared to H3N2.
- H1N1 in H1 seeders and H3N2 in H3 seeders and the inocula generally exhibited higher nucleotide diversity than the contact pigs
- Both H1N1 and H3N2 virus populations in seeder and contact pigs were predominantly shaped by genetic drift and purifying selection.
- There were no SNVs located in H1 and H3 antigenic regions in the PRIME BOOST pigs
- There were significantly more nonsynonymous mutations in the H1 antigenic region in SINGLE LAIV pigs and H1 seeders, showing signs of positive selection
- More genetic distance was found between SINGLE LAIV and seeder H1N1 viruses than between NO VAC and seeder H1N1 viruses. A single injection of a live attenuated vaccine (not matched to the inocula) could lead to the selection of H1N1 variants, potentially due to the low levels of HA-specific antibodies.
- Vaccinated and NO VAC pigs had a similar proportion of shared H1N1 variants with the seeder pigs showing the limited impact of vaccination on variant transmission in this study.
- Vaccinated pigs shared less H3N2 variant diversity with seeder pigs compared to the NO VAC pigs suggesting that de-novo mutations contributed more to the genetic variations of the H3N2 virus in contact pigs.
Abstract
Global evolutionary dynamics of influenza A virus (IAV) are fundamentally driven by the extent of virus diversity generated, transmitted, and shaped in individual hosts. How vaccination affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs is unknown. To evaluate the effect of vaccination on the transmission of genetically distinct IAV variants and their diversity after transmission in pigs, we examined the whole genome of IAV recovered from the nasal cavities of pigs vaccinated with different influenza immunization regimens after being infected simultaneously by H1N1 and H3N2 IAVs using a seeder pig model. We found that the seeder pigs harbored more diversified virus populations than the contact pigs. Among contact pigs, H3N2 and H1N1 viruses recovered from pigs vaccinated with a single dose of an unmatched modified live vaccine generally accumulated more extensive genetic mutations than non-vaccinated pigs. Furthermore, the non-sterilizing immunity elicited by the single-dose-modified live vaccine may have exerted positive selection on H1 antigenic regions as we detected significantly higher nonsynonymous but lower synonymous evolutionary rates in H1 antigenic regions than non-antigenic regions. In addition, we observed that the vaccinated pigs shared significantly less proportion of H3N2 variants with seeder pigs than unvaccinated pigs. These results indicated that vaccination might reduce the impact of transmitted influenza variants on the overall diversity of IAV populations harbored in recipient pigs and that within-host genetic selection of IAV is more likely to occur in pigs vaccinated with improperly matched vaccines.