scholarly journals Efficacy of Heterologous Prime-Boost Vaccination with H3N2 Influenza Viruses in Pre-Immune Individuals: Studies in the Pig Model

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 968
Author(s):  
Sharon Chepkwony ◽  
Anna Parys ◽  
Elien Vandoorn ◽  
Koen Chiers ◽  
Kristien Van Reeth

In a previous study in influenza-naïve pigs, heterologous prime-boost vaccination with monovalent, adjuvanted whole inactivated vaccines (WIV) based on the European swine influenza A virus (SwIAV) strain, A/swine/Gent/172/2008 (G08), followed by the US SwIAV strain, A/swine/Pennsylvania/A01076777/2010 (PA10), was shown to induce broadly cross-reactive hemagglutination inhibition (HI) antibodies against 12 out of 15 antigenically distinct H3N2 influenza strains. Here, we used the pig model to examine the efficacy of that particular heterologous prime-boost vaccination regimen, in individuals with pre-existing infection-immunity. Pigs were first inoculated intranasally with the human H3N2 strain, A/Nanchang/933/1995. Seven weeks later, they were vaccinated intramuscularly with G08 followed by PA10 or vice versa. We examined serum antibody responses against the hemagglutinin and neuraminidase, and antibody-secreting cell (ASC) responses in peripheral blood, draining lymph nodes, and nasal mucosa (NMC), in ELISPOT assays. Vaccination induced up to 10-fold higher HI antibody titers than in naïve pigs, with broader cross-reactivity, and protection against challenge with an antigenically distant H3N2 strain. It also boosted ASC responses in lymph nodes and NMC. Our results show that intramuscular administration of WIV can lead to enhanced antibody responses and cross-reactivity in pre-immune subjects, and recall of ASC responses in lymph nodes and NMC.

npj Vaccines ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Kristien Van Reeth ◽  
José Carlos Mancera Gracia ◽  
Ivan Trus ◽  
Lieve Sys ◽  
Gerwin Claes ◽  
...  

2020 ◽  
Author(s):  
Elana Raaphorst ◽  
Abdolvahab Farzan ◽  
Robert M. Friendship ◽  
Brandon N. Lillie

Abstract Background Porcine reproductive and respiratory syndrome, swine influenza, and mycoplasmal pneumonia are some of the most prevalent respiratory diseases affecting swine farm productivity in Canada. Monitoring for the prevalence of the infectious agents associated with these diseases on farm may help to improve herd-specific control strategies and to minimize the impact of disease on commercial swine farms. The objectives of this study were to investigate antibody responses to porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus (IAV), and Mycoplasma hyopneumoniae ( M. hyopneumoniae ) from weaning to the end of the finisher stage on a subset of commercial swine farms in Ontario and to examine the effects of nursery diet on antibody responses. Results Serology found 8, 61, and 31% of pigs at weaning, 1, 31, and 22% at the end of nursery, 8, 38, and 18% at the end of grower, and 11, 48, and 25% at the end of the finisher stage tested seropositive for PRRSV, IAV, and M. hyopneumoniae, respectively. Of the groups tested for PRRSV, IAV, and M. hyopneumoniae, 3, 14, and 5 groups had > 20% of pigs that tested seropositive at least once over the course of production (“high seropositivity”). In general, seropositivity was more likely to be lower at the end of nursery compared to the other production stages for all three pathogens, and more likely to be higher for PRRSV and IAV at weaning, end of grower, and end of finisher. Pigs that were seropositive for PRRSV were more likely to be seropositive forM. hyopneumoniae (p < 0.001). Overall, pigs fed a low complexity diet during nursery were more likely to be seropositive for PRRSV (p < 0.001) and IAV (p = 0.04). Conclusions This study provides information regarding changes in serum antibody in pigs across different stages of production and highlights periods of vulnerability. Additionally, these findings may encourage further research into the effects of nursery diet complexity on disease susceptibility and immune response.


2011 ◽  
Vol 92 (12) ◽  
pp. 2871-2878 ◽  
Author(s):  
Javier A. Cappuccio ◽  
Lindomar Pena ◽  
Marina Dibárbora ◽  
Agustina Rimondi ◽  
Pablo Piñeyro ◽  
...  

Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The current study describes the clinical epidemiology, pathology, and molecular and biological characteristics of the virus. Phylogenetic analysis revealed that the virus isolate shared nucleotide identities of 96–98 % with H3N2 IAVs that circulated in humans from 2000 to 2003. Antigenically, sera from experimentally inoculated animals cross-reacted mainly with non-contemporary human-origin H3N2 influenza viruses. In an experimental infection in a commercial swine breed, the virus was of low virulence but was transmitted efficiently to contact pigs and caused severe disease when an infected animal acquired a secondary bacterial infection. This is the first report of a wholly human H3N2 IAV associated with clinical disease in pigs in South America. These studies highlight the importance of two-way transmission of IAVs and SIVs between pigs and humans, and call for enhanced influenza surveillance in the pig population worldwide.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1388
Author(s):  
Joseph Eiden ◽  
Gilad Gordon ◽  
Carlos Fierro ◽  
Renee Herber ◽  
Roger Aitchison ◽  
...  

M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Janice R. Ciacci Zanella ◽  
Amy L. Vincent ◽  
Eraldo L. Zanella ◽  
Alessio Lorusso ◽  
Crystal L. Loving ◽  
...  

Influenza A viruses cause acute respiratory disease in swine. Viruses with H1 hemagglutinin genes from the human seasonal lineage (-cluster) have been isolated from North American swine since 2003. The objective of this work was to study the pathogenesis and transmission of -cluster H1 influenza viruses in swine, comparing three isolates from different phylogenetic subclusters, geographic locations, and years of isolation. Two isolates from the 2 subcluster, A/sw/MN/07002083/07 H1N1 (MN07) and A/sw/IL/00685/05 H1N1 (IL05), and A/sw/TX/01976/08 H1N2 (TX08) from the 1 sub-cluster were evaluated. All isolates caused disease and were transmitted to contact pigs. Respiratory disease was apparent in pigs infected with MN07 and IL05 viruses; however, clinical signs and lung lesions were reduced in severity as compared to TX08. On day 5 following infection MN07-infected pigs had lower virus titers than the TX08 pigs, suggesting that although this H1N1 was successfully transmitted, it may not replicate as efficiently in the upper or lower respiratory tract. MN07 and IL05 H1N1 induced higher serum antibody titers than TX08. Greater serological cross-reactivity was observed for viruses from the same HA phylogenetic sub-cluster; however, antigenic differences between the sub-clusters may have implications for disease control strategies for pigs.


2013 ◽  
Vol 94 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Marine L. B. Hillaire ◽  
Stella E. Vogelzang-van Trierum ◽  
Joost H. C. M. Kreijtz ◽  
Gerrie de Mutsert ◽  
Ron A. M. Fouchier ◽  
...  

Virus-specific CD8+ T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8+ T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8+ T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8+ T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.


2010 ◽  
Vol 11 (1) ◽  
pp. 81-96 ◽  
Author(s):  
Wenjun Ma ◽  
Jürgen A. Richt

AbstractSwine influenza is an important contagious disease in pigs caused by influenza A viruses. Although only three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, predominantly infect pigs worldwide, it is still a big challenge for vaccine manufacturers to produce efficacious vaccines for the prevention and control of swine influenza. Swine influenza viruses not only cause significant economic losses for the swine industry, but are also important zoonotic pathogens. Vaccination is still one of the most important and effective strategies to prevent and control influenza for both the animal and human population. In this review, we will discuss the current status of swine influenza worldwide as well as current and future options to control this economically important swine disease.


2017 ◽  
Vol 22 (47) ◽  
Author(s):  
Aeron Hurt ◽  
Naomi Komadina ◽  
Yi-Mo Deng ◽  
Matthew Kaye ◽  
Sheena Sullivan ◽  
...  

For over a decade virtually all A(H3N2) influenza viruses have been resistant to the adamantane class of antivirals. However, during the 2017 influenza season in Australia, 15/461 (3.3%) adamantane-sensitive A(H3N2) viruses encoding serine at residue 31 of the M2 protein were detected, more than the total number identified globally during the last 6 years. A return to wide circulation of adamantane-sensitive A(H3N2) viruses would revive the option of using these drugs for treatment and prophylaxis.


2009 ◽  
Vol 14 (21) ◽  
Author(s):  
A Solovyov ◽  
G Palacios ◽  
T Briese ◽  
W I Lipkin ◽  
R Rabadan

In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia.


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