Abstract
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.
Highlights
IntroductionNeuraminidase (NA) proteins derived from H3N2 viruses that once circulated in humans [1,2]
All swine influenza A viruses (SwIAV) of the H3N2 subtype have their hemagglutinin (HA)and neuraminidase (NA) proteins derived from H3N2 viruses that once circulated in humans [1,2].Repeated transmissions of distinct human-origin viruses to swine have led to an increase in the genetic diversity of SwIAV globally, with strains being confined to their geographical regions of introduction [3]
We examined the breadth of serum hemagglutination inhibition (HI) and neuraminidase inhibition (NI) antibody responses and protection against challenge after heterologous prime-boost vaccination of infection-immune pigs
Summary
Neuraminidase (NA) proteins derived from H3N2 viruses that once circulated in humans [1,2]. Repeated transmissions of distinct human-origin viruses to swine have led to an increase in the genetic diversity of SwIAV globally, with strains being confined to their geographical regions of introduction [3]. H3N2 SwIAV that circulate in European pigs were derived from a human virus that was circulating in the mid-1970s [4]. American pigs were derived from antigenically distinct human viruses that circulated in the 1990s and in the recent past, in 2011 [1]. This has resulted in the existence of distinct lineages and clusters of. These SwIAV have continued to evolve independently from their human counterparts, through either antigenic drift (mutations occurring in genes) or genetic
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