Inactivated PRRSV-2 vaccine reduces lung damage but not systemic infection

A high-dose, homologous inactivated vaccine against a Korean NADC34-like strain of porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) reduced fever, lung viral loads and pulmonary lesions in experimentally challenged piglets, but it did not produce a consistent reduction in blood virus or viral persistence in lymphoid tissues. The controlled study used 3-week-old, PRRSV-seronegative crossbred pigs and found that the strongest effects were associated with vaccine formulations containing a carbomer-and-squalene adjuvant. These findings indicate partial, tissue-specific protection rather than sterilizing immunity against infection.

Researchers from the Animal and Plant Quarantine Agency in South Korea prepared the vaccine from prrsv23-8s8n, a PRRSV-2 isolate recovered from a Korean farm in 2023. They challenged vaccinated animals with a second Korean isolate, prrsv23-9s15n, that belonged to the same Lineage 1, Sublineage 1.5 NADC34-like group. Although the two viruses were not identical, full-genome and ORF5 sequence analyses showed 97.50% and 97.01% nucleotide identity, respectively, supporting the experiment as a homologous challenge with closely related viruses. The study was designed to test whether a lineage-matched inactivated antigen could reduce disease outcomes when pigs were exposed to a related contemporary Korean virus.

Both isolates carried molecular features associated with NADC34-like viruses. Each contained a continuous 100-amino-acid deletion in the nonstructural protein 2 (NSP2) region, and recombination analyses indicated mosaic genomes containing segments derived from the VR2332 lineage 5 reference virus and NADC30-like viruses. Their shared genetic background was relevant to the study because NADC34-like variants have become increasingly prevalent in East Asia, while their rapid evolution and ability to evade host immune responses have raised concern about the protection supplied by older commercial vaccines. The researchers also noted that neither commercial inactivated vaccine nor a lineage-matched commercial reference was included, so the experiment compared different adjuvant formulations with an antigen-only group and unvaccinated controls rather than testing a commercial PRRSV-2 vaccine head to head.

Thirty pigs were randomly assigned to six groups of five. Four groups received 2 mL of inactivated vaccine intramuscularly, followed by a booster two weeks later. The experimental antigen was standardized to an equivalent of 10^8 TCID50 before inactivation and was delivered in a Carbopol 974P and squalene oil-in-water formulation, the same formulation supplemented with lipopolysaccharide, Montanide IMS1313, or phosphate-buffered saline without an adjuvant. A fifth group received no vaccine and was challenged as the control, while an unchallenged sixth group received sterile phosphate-buffered saline. At four weeks after the first vaccination, pigs in the five challenged groups received an intranasal inoculum containing 10^6 TCID50/mL of prrsv23-9s15n, with 1 mL administered into each nostril. No vaccine-related local or systemic adverse reactions were observed after either the primary or booster vaccination under these experimental conditions.

The challenge produced signs consistent with acute PRRS infection. Control pigs developed elevated rectal temperatures, and some exceeded 41.0 °C. Pigs receiving the Carbopol-only formulation maintained significantly lower temperatures than controls at several post-challenge time points, while the Carbopol-plus-lipopolysaccharide group had a profile similar to the controls early after challenge but lower temperatures from day 9 onward. No statistically significant temperature differences were detected for the Montanide or antigen-only groups. Mean body weight rose in every group, and neither average daily weight gain nor body weight differed consistently between vaccinated groups and the challenge control. The study therefore demonstrated a limited effect on the measured clinical outcomes rather than a general improvement in growth performance.

Binding antibody responses were detected after vaccination, with significant seroconversion in the Carbopol group by 14 days after the first dose. After challenge, vaccinated pigs had higher PRRSV-specific IgG sample-to-positive ratios than controls at day 4, with the Carbopol group remaining above controls through day 7. Nevertheless, no neutralizing antibodies were detected at the assay’s 1:2 limit in any group. Interferon-gamma ELISPOT responses increased in every challenged group, but vaccinated pigs did not differ significantly from challenge controls at any measured time point. The investigators therefore could not clearly attribute the cellular response observed after infection to vaccination rather than the challenge itself. The results show that induction of binding antibodies and infection-associated cellular responses did not, in this experiment, translate into detectable neutralizing activity or broad systemic viral suppression.

Systemic virology differed from the pulmonary outcomes. Blood viral loads in all challenged animals peaked at seven days after challenge and declined by day 21, but no vaccinated group showed a consistent or statistically significant reduction relative to controls. Viral shedding was detected in nasal swabs from all vaccinated groups. Although shedding was initially undetectable in the Carbopol group, the difference was transient and did not persist through the peak shedding period. Viral loads in the tonsils, mesenteric lymph nodes and inguinal lymph nodes were comparable among the challenged groups. The experiment therefore did not show that vaccination prevented infection, cleared circulating virus or restricted persistence in systemic lymphoid tissues. The relatively low blood viral loads measured in the challenge control also limited the study’s ability to detect differences in systemic virology, although the control animals showed fever and other outcomes consistent with successful infection.

Protection was more evident in the lungs. At necropsy 21 days after challenge, the Carbopol group had a significantly lower pulmonary viral load than the challenge control. The Carbopol-plus-lipopolysaccharide group had a numerically lower value that did not reach statistical significance. The Carbopol group also had lower macroscopic lung-lesion scores, while both carbomer-and-squalene groups had significantly lower microscopic interstitial-pneumonia scores. The consistency between reduced lung viral load and reduced histological injury in the Carbopol group suggests that this formulation partly limited viral activity in respiratory tissue. The antigen-only and Montanide groups did not show the same pattern of significant protection, underscoring the importance of formulation rather than antigen alone in this experiment. The pulmonary findings were nevertheless restricted to tissue-level outcomes and were not accompanied by significant changes in systemic virological parameters.

The results also demonstrate why a single endpoint can give an incomplete assessment of PRRSV vaccine performance. A vaccine may appear ineffective when judged by blood viremia or nasal shedding yet still reduce disease in lung tissue. In this study, fever, lung virus and lung pathology improved in some vaccinated groups even though systemic viral kinetics did not. Conversely, binding IgG and infection-associated interferon-gamma responses did not produce detectable neutralizing activity or complete systemic suppression. The study used a small experimental group, observed substantial animal-to-animal variation in lesion scores and did not include a commercial inactivated PRRSV-2 vaccine as an active reference; the only inactivated product available in South Korea was a PRRSV-1 vaccine that the investigators considered genetically unsuitable for that comparison. The results therefore describe the performance of this specific formulation under a controlled homologous challenge and do not establish field effectiveness or protection against genetically diverse challenge viruses.

PRRSV is an enveloped, positive-sense, single-stranded RNA virus in the Arteriviridae family, and the NADC34-like viruses examined here carried a characteristic NSP2 deletion. Existing inactivated vaccines do not contain replicating virus and therefore avoid some risks associated with modified-live products, but they have historically provided limited protection, even in homologous challenge studies. The new results support a narrower role for inactivated vaccination: a lineage-matched, high-titer antigen combined with a carbomer-and-squalene formulation may lessen clinical fever and pulmonary injury without eliminating infection or systemic persistence. The investigators proposed optimizing adjuvant systems, improving cellular and respiratory-tract immune responses and examining prime–boost strategies as possible directions for further vaccine development. Those proposals remain research directions; the present study does not demonstrate sterilizing immunity, improved growth, prevention of infection or protection in field herds.

Subject of Research: Evaluation of a homologous inactivated NADC34-like PRRSV-2 vaccine in experimentally challenged pigs

Article Title: A homologous NADC34-like PRRSV-2 inactivated vaccine partially modulates pulmonary viral load and pathological lesions under controlled challenge conditions

Article References: You, S.-H., Lee, H.-J., Song, S.-M., Shin, E.-G., Kim, J.-M., Shin, Y.-K., & Kang, S.-J. (2026). A homologous NADC34-like PRRSV-2 inactivated vaccine partially modulates pulmonary viral load and pathological lesions under controlled challenge conditions. Frontiers in Veterinary Science, 13, Article 1932482. https://doi.org/10.3389/fvets.2026.1932482

Image Credits: AI Generated

DOI: 10.3389/fvets.2026.1932482

Keywords: PRRSV-2, NADC34-like virus, inactivated vaccine, swine infectious disease, pulmonary pathology, carbomer adjuvant, viral challenge, pig immunology, homologous challenge, adjuvanted vaccine, homologous, NADC34-like