Poultry Vaccination - Photo Credit OIE
#14,305
The welcomed lull in avian flu activity around the world these past couple of years, driven largely by massive poultry vaccination campaigns in China (and other nations), has seemingly granted - if not a reprieve - at least a temporary restraining order against an avian flu pandemic.
Considering the H7N9 abyss we were staring into two years ago (see NPR: A Pessimistic Guan Yi On H7N9's Evolution), it's hard not to consider that a big win.But, as we saw last April in OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign, in most cases these viruses weren't eliminated, only suppressed. While the immediate impact of poultry vaccination in China have been overwhelmingly positive, the long-term impacts are still under review.
Poultry vaccines don’t always prevent disease – sometimes they only mask the symptoms of infection.Poorly matched vaccines can enable viruses to spread stealthily, and continue to evolve into newer, less vaccine-affected strains (see The HPAI Poultry Vaccine Dilemma). Sadly, the evidence suggests many countries are using suboptimal or outdated poultry vaccines.
In the past year we've started to see a few cracks in China's bird flu veneer, particularly with HPAI H5N6 (see Hong Kong CHP Notified Of A Human H5N6 Case In Beijing), which may indicate some `drift' in the circulating viruses away from the vaccine.
While avian H7N9 and H5N6 in China are our two biggest avian flu worries, they are far from alone.
- H5 Clade 2.3.2.1c continues to spread in the Middle East, Africa, India, China, and undoubtedly other parts of Asia
- Clade 2.3.4.4 H5 viruses have diverged into multiple subtypes and spread globally
- LPAI H9N2 continues to evolve, acquired mammalian adaptations, and reassort with other viruses
- H7N3 has plagued Mexico intermittently for the past 7 years
- And we've a growing array of H4, H6, H7 and H10 viruses are also on our radar
The H7N3 outbreak in Mexico is of interest - not only because it impacts our southern neighbor and could be carried north by migratory birds - but because we know of a couple of `mild' human infections with this strain (see MMWR: Mild H7N3 Infections In Two Poultry Workers - Jalisco, Mexico).
While not unheard of, prior to 2013, known avian H7 infections in humans had been overwhelmingly mild (see A Brief History Of H7 Avian Flu Infections). Since then, the emergence of H7N9 (and H7N4) in China has elevated H7's threat profile.Like China, after suffering massive losses, Mexico employed an H7 poultry vaccine campaign - and since 2013 outbreaks have been greatly reduced - although not entirely eliminated (see latest OIE Report).
Today we've a fascinating paper, published in PLoS One, that tracks the rapid evolution and diversification of avian H7N3 in Mexico since 2012, producing at least three genetically distinct clusters of viruses.
The authors speculate these changes may have been driven by a number of factors, including host adaptations while carried by poultry in a confined space, and potentially, vaccine driven escape mutations.I've only reproduced a few excerpts from a lengthy, and detailed, research paper. So you'll want to follow the link to read it in its entirety. When you return, I'll have a brief postscript.
Research Article
Rapid evolution of Mexican H7N3 highly pathogenic avian influenza viruses in poultry
Sungsu Youk , Dong-Hun Lee , Helena L. Ferreira, Claudio L. Afonso, Angel E. Absalon, David E. Swayne, David L. Suarez, Mary J. Pantin-Jackwood
Published: September 12, 2019 https://doi.org/10.1371/journal.pone.0222457
Abstract
Highly pathogenic avian influenza (HPAI) virus subtype H7N3 has been circulating in poultry in Mexico since 2012 and vaccination has been used to control the disease. In this study, eight Mexican H7N3 HPAI viruses from 2015–2017 were isolated and fully sequenced.
No evidence of reassortment was detected with other avian influenza (AI) viruses, but phylogenetic analyses show divergence of all eight gene segments into three genetic clusters by 2015, with 94.94 to 98.78 percent nucleotide homology of the HA genes when compared to the index virus from 2012. The HA protein of viruses from each cluster showed a different number of basic amino acids (n = 5–7) in the cleavage site, and six different patterns at the predicted N-glycosylation sites.
Comparison of the sequences of the Mexican lineage H7N3 HPAI viruses and American ancestral wild bird AI viruses to characterize the virus evolutionary dynamics showed that the nucleotide substitution rates in PB2, PB1, PA, HA, NP, and NS genes greatly increased once the virus was introduced into poultry.
The global nonsynonymous and synonymous ratios imply strong purifying selection driving the evolution of the virus. Forty-nine positively selected sites out of 171 nonsynonymous mutations were identified in the Mexican H7N3 HPAI viruses, including 7 amino acid changes observed in higher proportion in North American poultry origin AI viruses isolates than in wild bird-origin viruses.
Continuous monitoring and molecular characterization of the H7N3 HPAI virus is important for better understanding of the virus evolutionary dynamics and further improving control measures including vaccination.
(SNIP)
Vaccination was widely instituted in Mexico using the LPAI virus A/Cinnamon Teal/Mexico/2817/2006(H7N3) which experimentally was shown to be protective from challenge with the virulent virus. The nucleotide sequence relatedness between this wild bird origin vaccine strain and the field HPAI strains varied from 90.5% to 98.1% for all gene segments, and likely provided opportunities for greater virus replication and opportunities for positive selection [10].
This vaccine although protective early on, appeared to have reduced effectiveness after just a few years. Although a direct association between H7N3 vaccination and virus evolution has not been fully established, there is evidence that addition of N-glycosylation sites contributed to the escape of 2015 Mexican H7N3 HPAI from vaccine-induced immunity [16].
In addition, considering that the AI virus evolves more rapidly in domestic poultry than in wild birds, the high evolution rate and dn/ds ratio of HA in the Mexican poultry viruses, which is comparable to the rate of Italian H7N1 and Indonesian H5N1 outbreaks, may also imply selective pressure caused by vaccine-induced immunity [40, 48].
(SNIP)
This study is the first analysis demonstrating the evolution of the Mexican H7N3 HPAI after five years of circulation in poultry. After introduction of the Mexican H7N3 HPAI virus to poultry the viral genome has changed greatly above the normal global substituion rate, with a strong negative selection.
As a consequence, the virus has diversified into three clusters with genetic variations in HA cleavage sites. Amino acids changes that are positively selected in the H7N3 virus suggest adaptation to poultry and possible vaccine escape mutations as mechanisms of change during the virus evolution.
Continuous monitoring and genetic analysis are needed to better understand the evolution of HPAI viruses persisting in poultry and to control the virus spread.
(Continue . . )
China has shown that properly applied and up-to-date poultry vaccines can have a positive impact on the spread of avian flu. At least in the short term. We'll have to wait a few years to see if there are any negative long-term ramifications.
To be effective, however, poultry vaccines must be continually updated, and coverage has to be extensive - otherwise they only hide the problem - giving viruses opportunities to evolve.Some past blogs on suboptimal poultry vaccination, and their impact include:
Two Studies On The Recent Evolution Of HPAI H5 Viruses In The Middle East
JID: Antigenic Drift of H7N9 Viral Hemagglutinin
Sci. Reports: Efficacy Of AI Vaccines Against The H5N8 Virus in Egypt
Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China).
Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens
EID Journal: Subclinical HPAI In Vaccinated Poultry – China
