Heguang Forum / Study on Nutritional Strategies to Reduce PEDV Viral Load During the Nursery Phase

Abstract: Following the implementation of policies banning antibiotics in feed and reducing antibiotic use in livestock production, managing animal viral diseases has become relatively complex. For example, in piglets, preventing large-scale outbreaks of viruses such as PEDV and PRRSV is a pressing challenge. Traditionally, we have relied primarily on vaccines to control viral occurrence and transmission; however, due to the rapid mutation rates of viral strains and their elusive nature, coupled with occasional vaccine failure, it is essential—while continuing to develop and deploy vaccines—to also select specific antiviral agents (such as medium-chain fatty acids) based on viral structure and transmission characteristics, from a zootechnical perspective. These agents can interfere with the activity of key proteins involved in the viral replication cycle, irreversibly inhibiting viral activity, enhancing innate immunity in animals, and thereby boosting their overall antiviral capacity.

This paper briefly describes an experiment investigating the antiviral effects of an antiviral acid—developed based on Lewis acid–base electronic theory—when incorporated into creep feed for piglets. The results indicate that: (1) the antiviral acid exhibits a high inhibition rate against PEDV both in vivo and in vitro; (2) it effectively alleviates pathological damage caused by PEDV and other viral infections; (3) it promotes the expression of host cytokines and, following field virus challenge, suppresses the expression of pro-inflammatory cytokines; (4) it enhances the secretion of anti-inflammatory cytokines, strengthens the mucosal barrier, and boosts the animal’s innate immunity. These findings suggest that an antiviral acid formulated with carefully selected Lewis acids (such as medium-chain fatty acids) as key components, when used in creep feed, delivers robust antiviral efficacy and can serve as a valuable adjunct to vaccination in routine production practices.

Keywords: Antibiotic-free; weaned piglets; antiviral acid; medium-chain fatty acids; nonspecific immunity

During the creep-feeding and nursery phases, piglets are particularly susceptible to bacterial and viral infections because their physiological and immune systems are not yet fully developed. Diseases such as porcine reproductive and respiratory syndrome (PRRS), transmissible gastroenteritis (TGE), and pseudorabies are common viral causes of mortality in piglets. Current strategies for controlling and eradicating these viruses rely primarily on vaccination; however, vaccination has certain limitations. Some pigs exhibit poor immune responses, compromising vaccine efficacy, while others harbor highly variable pathogens that existing vaccines cannot fully protect against. For example, since December 2011, the incidence of PRV in China has increased, with outbreaks of pseudorabies occurring even in farms where large numbers of pigs had been vaccinated. Thus, in addition to vaccination, it is essential to bolster piglets’ innate immunity through nutritional interventions to counter evolving viral strains and other complications arising from viral carriage.

Medium-chain fatty acids (MCTs) refer to saturated fatty acids containing 6–12 carbon atoms and their monoacylglycerols. Nutritionally, the term typically specifies even-numbered carboxylic acids such as caproic, caprylic, capric, and lauric acids; some classifications also include myristic acid. Research indicates that MCTs exhibit significant antiviral effects and exert favorable regulatory and inhibitory actions on animal physiology and pathogens. For example, Li et al. (2009), in a study published in Nature, formulated GML into a gel preparation and conducted vaginal gel administration trials in rhesus macaques. The results demonstrated that GML effectively suppressed HIV viral activity and prevented HIV infection in these monkeys. Korean researchers led by Joshua (2020) confirmed that a combination of capric, caprylic, and lauric acids, along with lauric acid monoacylglycerol, exerts potent virucidal activity against African swine fever virus in feed and drinking water, with lauric acid monoacylglycerol displaying particularly strong antiviral efficacy. Jordan et al. (2019), by measuring the impact of varying concentrations of medium-chain fatty acids over different time periods on the Ct values of PEDV in complete feed, showed that these fatty acids can inhibit PEDV activity in commercial feed formulations.
 

However, the antiviral activity of MCTs varies: medium-chain fatty acid monoglycerides exhibit stronger antiviral effects than their corresponding fatty acids, with minimum inhibitory concentrations 5–10 times lower (HALLDOR THORMAR, 1987). Among monoglycerides, different compounds also show varying antiviral potencies at equivalent doses; for example, a study by Hilmarsson (2005) demonstrated that caprylic acid monoglyceride rapidly inhibits viruses and outperforms lauric acid monoglyceride. These findings indicate that MCTs possess significant antiviral activity, but this is influenced by the specific medium-chain fatty acids and the composition and ratios of the monoglycerides. Additionally, research suggests that MCTs exert their antiviral effects only upon direct contact with the virus, blocking viral attachment to host cells. In contrast, medium-chain fatty acids are rapidly metabolized in animals; low inclusion levels make it difficult to deliver sufficient amounts to viral attachment sites, while high levels can lead to ketone production during metabolism, resulting in acidosis.

I. In vitro experiments

A defined dose of PEDV was inoculated into creep feed, with antiviral acid added at 0, 0.25, 0.5, 1.0, and 2.0 g/kg, respectively. The feed was stored for 7 days, and the viral load was assessed. The results showed that as storage time increased, the PEDV load in the feed decreased in a dose-dependent manner, indicating that adding antiviral acid to creep feed can significantly reduce the viral load.

Figure 2. Changes in feed viral load after adding antiviral acid to creep feed

II. In vivo experiments

The experiment was divided into five groups: a control group, a PEDV-infected group, and high-, medium-, and low-dose antiviral acid treatment groups, with five piglets per group. Seven-day-old piglets orally inoculated to establish the PEDV model rapidly developed typical symptoms of vomiting and diarrhea. Piglets in the antiviral acid treatment groups were immediately administered the antiviral acid via feed for one consecutive week, twice daily. Body weight, feed intake, and clinical signs were recorded. At the end of the trial, all piglets were euthanized, and blood, major visceral organs, the intestine, and intestinal contents were collected for analysis of relevant immune parameters.

2.1 Clinical Signs and Body Weight Changes in Piglets After Antiviral Acid Feeding

Following viral challenge, all piglets exhibited vomiting and watery diarrhea; the model group rapidly became dehydrated and emaciated, with their entire bodies contaminated by vomitus and feces, and they progressed to collapse and near death during the experiment. The control group pigs were housed in isolation and maintained good growth. In the low-dose antiviral acid group, clinical signs resembled those of the model group, but without collapse, and recovery was gradual over time. Pigs treated with medium and high doses did not vomit; in the high-dose group, some pigs experienced transient diarrhea that resolved quickly, demonstrating a favorable antiviral effect. Furthermore, the piglets tolerated antiviral acid well, with no signs of toxicity.

Following viral challenge, piglets in the model group rapidly became dehydrated and emaciated; vomiting and diarrhea led to anorexia and refusal to eat. Body weight continued to decline throughout the observation period without recovery. Piglets in the control group exhibited robust feed intake and good weight gain. In the antiviral acid group, the high dose demonstrated a significant antiviral effect: piglets showed markedly improved appetite and evident physical recovery, with body weight beginning to increase on day 4; moreover, the high dose was more effective than the medium dose (see Figure 3).

Figure 3. Body weight changes in piglets fed antiviral acidified feed

2.2 Histopathological Examination Results of Piglets

The small intestine is the primary site of injury following PEDV infection, with lesions predominantly observed in the jejunum and ileum (see Figure 4), while changes in the duodenum are less pronounced (data not shown). In piglets infected with PEDV, the jejunal mucosa becomes thinned, intestinal villi atrophy or even detach, and inflammatory cell infiltration occurs; treatment with antiviral acid markedly promotes recovery of villous architecture. In the ileum, PEDV infection is characterized by a reduction in lymphoid follicles, villous atrophy and shedding, and hemorrhage; administration of antiviral acid results in significant amelioration of these lesions.

Figure 4. Histopathological changes in the jejunum and ileum of piglets after feeding with antiviral acidic feed (HE ×400)

2.3 Immunoglobulin Expression Levels in Blood

Immunoglobulins in the blood are direct indicators of humoral immune status. Following PEDV infection in piglets, the levels of IgG, IgM, and IgA in the blood were all significantly reduced. After treatment with antiviral acid, the level of IgM in the blood increased significantly, with all three doses proving effective in a dose-dependent manner. This indicates that antiviral acid can effectively induce early antibody production and enhance the host’s defense against viral infection. Furthermore, at medium and high doses, antiviral acid significantly upregulated the expression of immunoglobulins IgG and IgA, thereby strongly promoting the host’s ability to clear the pathogen; results are shown in Figure 5.

Figure 5. Changes in the levels of three immunoglobulins in the blood of piglets after feeding with antiviral acidic feed.

2.4 Results of Inflammatory Cytokine Detection in Jejunal Tissue

Moderate inflammation is essential for clearing infections, but excessive activation of inflammatory cells releasing large amounts of cytokines can hinder tissue repair. Following PEDV infection in piglets, numerous types of cytokines are simultaneously released, causing severe damage to intestinal tissues, including IL-1β, IL-6, TNF-α, IL-2, IL-10, and the inhibitory immune factor IL-17. After antiviral acid treatment in infected piglets, the expression levels of IL-1β and TNF-α in intestinal tissues were significantly reduced across all three dosage groups; additionally, IL-6 and IL-10 were significantly downregulated at medium and high doses, while the inhibitory immunomodulatory factor IL-17 was significantly decreased at the high dose, as shown in Figure 6. These results demonstrate that the antiviral acid can markedly attenuate the inflammatory response in the infected intestine, thereby promoting tissue repair.

Figure 6. Expression of inflammatory factors in the jejunum of piglets following antiviral acid feeding

Written by: Emperor Cheng

Review: Hu Youjun

Arranged by: Li Weitao