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Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions.

ABSTRACT: Influenza A virus (IAV) is one of the most important respiratory viruses affecting pig health and vaccination is the most common strategy to control influenza infections. In this field study we assessed the onset and duration of shedding of a live attenuated influenza virus (LAIV) vaccine, its ability to transmit to non-vaccinated pigs and whether the LAIV could be aerosolized and detected in the environment. Thirty-three litters (n = 33) of a farm using the LAIV vaccine were selected for the study, a subset of them (n = 12) were left unvaccinated and a subset of piglets (n = 3) in vaccinated litters were also left unvaccinated to serve as sentinels. Selected piglets from the litters were sampled multiple days post vaccination (DPV) by collecting nasal swabs and blood, and were tested using a LAIV vaccine specific RT-PCR assay and hemagglutination inhibition assay against the LAIV strains respectively. Environmental specimens consisting of air and surface wipes were also collected. One hundred percent (21/21) of the vaccinated litters tested LAIV positive 1 DPV and until 6 DPV. In contrast, only five (5/33) of the thirty-three non-vaccinated pigs tested positive during the course of the study. Viable LAIV was confirmed in vaccinated pigs by cell culture and whole genome sequencing. In addition, low levels of LAIV RNA (RT-PCR Ct values ranging between 33 and 38) were detected in all air specimens collected on the day of vaccination and until 6 DPV (3/10). Pigs had maternally derived antibodies reactive against the LAIV strains which may have influenced the degree of shedding observed. Under the conditions of this study, shedding of the LAIV from vaccinated pigs was limited in time, resulted in minimal transmission to non-vaccinated pigs and was detected in low levels in aerosols collected in the vaccinated rooms likely influenced by the presence of maternally derived antibodies against the LAIV strains.

SUBMITTER: Lopez Moreno G

PROVIDER: S-EPMC7877771 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions.

Lopez Moreno Gustavo G Nirmala Jayaveeramuthu J Goodell Christa C Culhane Marie M Torremorell Montserrat M

PloS one 20210211 2

Influenza A virus (IAV) is one of the most important respiratory viruses affecting pig health and vaccination is the most common strategy to control influenza infections. In this field study we assessed the onset and duration of shedding of a live attenuated influenza virus (LAIV) vaccine, its ability to transmit to non-vaccinated pigs and whether the LAIV could be aerosolized and detected in the environment. Thirty-three litters (n = 33) of a farm using the LAIV vaccine were selected for the st ...[more]

PMID: 33571263

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Project description:Natural killer T (NKT) cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses. Several studies have used this approach to adjuvant inactivated and subunit influenza A virus (IAV) vaccines, including to enhance cross-protective influenza immunity. However, less is known about whether α-GalCer can enhance live attenuated influenza virus (LAIV) vaccines, which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating influenza vaccines. The current study used the swine influenza challenge model to assess whether α-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine (TX98ΔNS1) encoding a truncated NS1 protein. In one study, weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0, 10, 50, and 100 μg/kg doses of α-GalCer, and subsequently challenged with a heterologous H3N2 virus. All treatment groups were protected from infection. However, the addition of α-GalCer appeared to suppress nasal shedding of the LAIV vaccine. In another experiment, pigs vaccinated with the H3N2 LAIV, with or without 50 μg/kg of α-GalCer, were challenged with the heterosubtypic pandemic H1N1 virus. Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways, and significantly decreased virus shedding. On the other hand, combining the vaccine with α-GalCer reduced cross-protective cellular and antibody responses, and resulted in higher virus titers in respiratory tissues. These findings suggest that: (i) high doses of α-GalCer impair the replication and nasal shedding of the LAIV vaccine; and (ii) α-GalCer might interfere with heterosubtypic cross-protective immune responses. This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.Supplementary informationThe online version contains supplementary material available at 10.1186/s44149-022-00051-x.

Project description:BackgroundPorcine epidemic diarrhea virus (PEDV) causes diarrhea in all ages of pigs with 50-100% mortality rates in neonatal piglets. In the United States, inactivated and subunit PEDV vaccines for pregnant sows are available, but fail to induce sufficient protection in neonatal piglets farrowed from PEDV naïve sows. A safe and efficacious live attenuated vaccine that can prime mucosal immune responses is urgently needed. In this study, we evaluated the safety and efficacy of two attenuated PEDV vaccine candidates, the emerging non-S INDEL PEDV strain PC22A at the 100th cell culture passage level - Clone no. 4 (P100C4) and at the 120th passage level (P120), in weaned pigs.ResultsFour groups of 40-day-old weaned pigs were inoculated orally with PEDV PC22A-P3 (virulent), -P100C4, -P120, and mock, respectively, and challenged with the P3 virus at 24 days post-inoculation (dpi). After inoculation, P3 caused diarrhea in all pigs with a high level of fecal viral RNA shedding. P100C4 and P120 did not cause diarrhea in pigs, although viral RNA was detected in feces of all pigs, except for one P100C4-inoculated pig. Compared with the P120 group, P3- and P100C4-inoculated pigs had higher serum PEDV-specific IgG and viral neutralizing (VN) antibody (Ab) titers at 14 dpi. After the challenge, no pigs in the P3 group but all pigs in the P100C4, P120, and mock groups had diarrhea. Compared with the P120 group, pigs in the P100C4 group had a more rapid decline in fecal PEDV RNA shedding titers, higher titers of serum PEDV-specific IgG, IgA, and VN Abs, and higher numbers of intestinal IgA Ab-secreting cells.ConclusionsPEDV PC22A P100C4 and P120 were fully attenuated in weaned pigs but failed to elicit protection against virulent P3 challenge. P100C4 induced higher PEDV-specific antibody responses than P120 post inoculation resulting in a greater anamnestic response post challenge. Therefore, P100C4 potentially could be tested as a priming vaccine or be further modified using reverse genetics. It also can be administered in multiple doses or be combined with inactivated or subunit vaccines and adjuvants as a PEDV vaccination regimen, whose efficacy can be tested in the future.

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Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions.

Publications

Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions.

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