Molecular characterization and antigenic prediction of foot-and- mouth disease virus in relation to vaccine improvement in endemic settings in Africa
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Date
2024-05
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Sokoine University of Agriculture
Abstract
Foot-and-mouth disease (FMD) affects all cloven-hoofed livestock
and wildlife, and it is caused by FMD virus (FMDV) that belongs to the
genus Aphthorvirus and family Picornaviridae. The disease threatens
food security and livelihoods across different parts of the world. There
are seven FMDV serotypes (O, A, C, Asia1, SAT1-3), and studies in
southern Africa describe buffalos to be persistently infected reservoirs
of SATs and transmit the viruses to cattle. The FMD control is
challenging and antigenic heterogeneity among field-circulating
strains represents the most significant factor. The field's infinite
variants pose a challenge to the effectiveness of vaccines and
suggests for quick, reliable, and cost-effective methods for obtaining
vaccine improvements relevant information timely. FMD is endemic in
Africa; impacting the livelihoods of pastoral communities, and hinders
the livestock sector by denying access of regional and global lucrative
markets. Currently, the strategies deployed to control FMD in Africa,
especially tropical Africa, are typically fragmented national-level
focused activities with relatively poor outcomes, rather than regionally
coordinated initiatives that have been used on other continents
(South America, Europe) to reduce and even eliminate virus
circulation. Studies have not demonstrated whether the buffalo can
also act as carrier of the EurAsian serotypes O and A occurring in
parts of East Africa. Also the current epidemiological status of the
field circulating strains and their genetic-antigenic characteristics
need to be understood. Also, it was unclear on the main challenges to
FMD control under pastoral dominated and endemic settings in Africa
that has hindered FMD control for decades.
This study investigated field reported outbreaks and clinically health
buffalo of Tanzania to determine the molecular epidemiology of the
circulating field strains between 2018 and 2021, their genetic-
antigenic characteristics, and their evolutionary relationships using
molecular techniques for
FMDV detection, typing,
and
characterization. The seroprevalence of FMDV serotypes O and A in
Tanzania were studied using NSP ELISA for natural infection
screening and typed by Solid phase competitive ELISA (SPCE) assay. Additionally; the B-cell antigenic epitopes of SAT1 types were
mapped by combined publicly available immuno-informatics
tools ranging from those employing propensity scales to the most
recent machine learning and artificial intelligence models, to
maximize the prediction authenticity, on the FMDV type SAT1 VP1
polypeptides from this study and those sourced from global rich
databases.
The study identified three FMDV serotypes (A, O and, SAT1)
circulating in the field as Africa Topotype G-I lineage, EA-2 Topotype,
and Topotype I (NWZ) respectively. This study nucleotide sequences
for serotypes O and SAT1 field strains were analysed categorically,
and the shared percent identities of 92.0-100.0% and 96.9-98.8%
were revealed respectively. The analysed 247 buffalo (37.6%, n =93)
and cattle (58.3%, n =154) NSP ELISA positive serum samples from
livestock-wildlife interface areas of Katavi, Mikumi, Mkomazi, and
Ruaha ecosystems in Tanzania were further analyzed for FMDV
serotype O and A by SPCE. A highest percentage seropositivity (PS)
was revealed (67%, n= 103) and (55%, n= 51) in cattle and buffalo,
whereas FMDV serotype A tested highest (54%, n= 83) and O (25%,
n= 23) for cattle and buffalo sera, respectively. Also, some of the
cattle (36%, n= 56) and buffalo (25%, n= 23) sera tested, showed
evidence of multiple infection with FMDV serotypes O and A. Results
showed that out of the 93 analyzed NSPE positive buffalo samples,
30.1% (28) of CI (19 – 39) had antibodies specific to FMDV Type A.
Also 54.8% (51) of CI (39 – 64) and 24.7% (23) of CI (15 – 33) had
antibodies specific to FMDV type O and those of mixed sero reaction
respectively. Similarly, out of 154 NSPE positive cattle samples
analyzed 53.9% (83) of CI (69 – 98), 66.9% (103) of CI (88 – 118)
and 36.4% (56) of CI (44 – 70) had FMDV antibodies specific to type
A, O, and mixed (O&A) seroreactions respectively. The results of
compared serotype-specific seroreactions statuses revealed higher
percentage for type O across all species, next type A, and the lowest
score for mixed seroreactions. Similarly; at 95% CI, the analyzed
cattle and buffalo NSPE positives expressed higher scores of (41.7%;
20.65%) by (33.6%; 11.34%) and (22.67%; 9.31%) on type O, type A
and mixed seroreactions respectively. Results on Chi-square test of
independence were significant, X2 (df = 4, N = 330) = 31.0876, p =.00001 at p<.05 criteria, indicating a relation between spp difference
and variation in state of FMDV infection rates. The analyzed probang
buffalo samples (n=89) from Serengeti national park using FMDV
serotype O and A specific primers (one-step RT-PCR), 1.2% was
revealed to be FMDV type O. Also, five consensus linear epitopes
(PLE I – V) at positions 3-30, 44-59, 95-112, 134-149, 199-219 with
75%, 88%, 94%, 44 % and 24% of their aa reads conserved were
observed respectively. Additionally; conformational epitopes (PCE I –
VI) at positions 1-26, 82-87, 93-114, 131-149, 175-179, and 201-221
with 53 – 100% conserved were also identified. As the vaccines are
challenged by the rapidly evolving FMDV in the field, the unveiling of
conserved epitope domains is vital for enhancing future FMDV
vaccines long-term effectiveness in the field.
This study has demonstrated FMDV type O infections in buffalo being
the first molecular and serosurvey combined study to be undertaken
on Eurasian FMDV types O and A in cattle and buffalos in Tanzania.
The information generated from this study strengthens knowledge on
FMDV epidemiology in Tanzania and Africa, and thereby contributing
to the progressive control pathway-FMD program through tailored
control initiatives. The unveiled challenges of FMD control amongst
Africa’s diverse pastoral communities’ landscape for triggering
strategical discussions on national and transboundary regional-based
FMD control approaches in Africa.
Description
PhD Thesis
Keywords
Molecular Characterization, Antigenic Prediction, Mouth Disease Virus, Vaccine Improvement -Endemic Settings, Africa