Key takeaways

• MetaStim adjuvant used in Fostera® Gold PCV MH provides a strong combination of humoral and cellular immunity against PCV2.²
• Fostera Gold PCV MH efficacy studies demonstrated 23 weeks of continuous protection for both PCV2 and Mhp, longer than any other PCV2 vaccine in the market.⁶
• Fostera Gold PCV MH is the only PCV2 bivalent vaccine in the US containing two PCV2 genotypes and in multiple field trials, it showed efficacy against PCV2d.^7-12

A porcine circovirus type 2 (PCV2) vaccine from Zoetis produces a robust and lasting cell-mediated immune response — the type of response that’s essential for protecting pigs against PCV2 disease.

Role of the adjuvant

“Why one vaccine induces stronger cell-mediated immunity (CMI) than another is largely due to the vaccine’s adjuvant — the substance added to vaccines to boost the immune response,” Meggan Bandrick, DVM, PhD stated.

The robust antibody response as well as a strong cell-mediated response is a product of the adjuvant MetaStim which is used in Fostera® Gold PCV MH. “Adjuvants are the instruction manual for the immune system,” said Dennis Foss, DVM, PhD, Research Director. They play an important role in determining the type of immunity activated. When properly paired with vaccines, adjuvants can steer the animal’s response toward the best, most effective type of immunity for a given pathogen. In a natural infection, the innate immune system recognizes the pathogen (via “molecular patterns”) or some effect of the pathogen (cell damage or death) and signals the immune system to respond appropriately. When pathogens are inactivated to make them safe for vaccines, some of these molecular patterns and effects are lost. Adjuvants replace these lost signals and allow the immune system to recognize and respond effectively to the vaccine.¹

During the development stage of Fostera Gold PCV MH, several adjuvants were evaluated. MetaStim was found to provide the best combination of humoral and cellular immunity against PCV2.² MetaStim is an oil-in-water emulsion with an oil content of less than 1% by volume. It provides a strong immune response with minimal adverse reactivity.³ Injection site reactions are rare and negligible, which was demonstrated in a large three-state field trial with Fostera Gold PCV MH.³ Vaccines with a high mineral oil content may induce a higher, immediate antibody response but less cellular immunity. The goal of the adjuvant selection was to induce the best balance of humoral and cellular immunity.

Why cell-mediated immunity matters

Assessments of vaccine responses tend to focus on antibody response, also known as humoral immunity, instead of cell-mediated immunity — often because antibodies are easier to measure. Humoral means body fluids. Humoral immunity involves the release of pathogen-fighting antibodies into serum or fluid. Cellular immunity happens by direct action of a cell.

Both types of immunity are important, Bandrick continued. “Antibodies, which are made from B cells, recognize and help neutralize circulating virus, but they can’t get to viruses that have gotten into cells. That’s where cell-mediated immunity comes in. T cells not only help B cells produce effective antibodies, they kill virus-infected cells and help clear infection,” she said.

Foss provides an example – PCV2 is a persistent virus that can hide out in some cells, such as macrophages, and then spreads, usually to lymph nodes. Ultimately, the virus replicates in lymphocytes and kills them, causing immune suppression. The pig is left susceptible to other infectious diseases.

Activating both humoral and cellular immunity provides a double whammy against PCV2. There is evidence that Mycoplasma hyopneumoniae (Mhp) can also persist in cells,⁴ which is one more reason why MetaStim was chosen for the adjuvant in Fostera Gold PCV MH.

Field Studies

Zoetis researchers evaluated cell-mediated immunity in pigs vaccinated with Fostera Gold PCV MH, the vaccine that protects against Mhp in addition to PCV2. They compared results to those from pigs given another commercial PCV2 vaccine and to control pigs that received only saline. The groups were treated as follows:

• Fostera Gold PCV MH split dose: 1 ml at 3 and 6 weeks of age
• Fostera Gold PCV MH one dose: 2 ml at 3 weeks of age
• Circumvent® PCV-M G2 split dose: 1 ml at 3 and 6 weeks of age
• Control: 1 ml saline at 3 and 6 weeks of age

Three weeks after the last vaccination was administered, pigs were challenged with virulent PCV2d because it’s the most prevalent PCV2 genotype in US herds.

“Pigs vaccinated with two doses of Fostera Gold PCV MH had a higher T-cell response than pigs vaccinated with Circumvent PCV-M G2 as seen in Figure 1,” said Bandrick. Even pigs that received only one dose of Fostera Gold PCV MH had higher T-cell response than pigs vaccinated twice with Circumvent PCV-M G2.²

In contrast, Circumvent PCV-M G2 induced very little detectable cell-mediated immunity. Bandrick explained that “a higher T-cell response after vaccination is associated with a longer duration of immunity,⁵ which is especially important with persistent viruses like PCV2.” In addition, the cell-mediated immune response was significantly higher compared to the response after two doses of a PCV2 vaccine with a different adjuvant.²

The development of humoral immunity was observed in pigs receiving two doses of either vaccine. In addition, pigs that received only one dose of Fostera Gold PCV MH showed a rapid PCV2 antibody response in challenged pigs, suggesting a robust priming of the humoral immune response with a single dose of Fostera Gold PCV MH.

* Vaccination induced a biologically relevant CMI response if above 50 SFC/10⁶ PBMC. Post-challenge, PCV2-specific T cells move into the tissues and out of the blood to protect against PCV2 infection.

The vaccine’s duration of immunity against PCV2 is 23 weeks, Bandrick said, and noted that the vaccine’s duration of immunity against Mhp is also 23 weeks.⁶ That’s longer than any other PCV2 vaccine in the US, which contain different adjuvants.

Cell-mediated immunity was evaluated with an enzyme-linked immunosorbant spot assay. The assay detected the number of lymphocytes isolated from blood that responded to the vaccines by secreting the cytokine interferon gamma (IFN-γ) when exposed to PCV2 antigen. “The strength of the PCV2-specific, IFN-γ response correlates with protective immunity,” she said. Serology demonstrated that pigs vaccinated with either regimen of Fostera Gold PCV MH or the other vaccine developed antibodies against PCV2, as expected, Bandrick noted.

Besides MetaStim, Fostera Gold PCV MH contains PCV2a and PCV2b. It’s the only commercial vaccine in the US with two PCV2 genotypes, and in multiple field trials, it showed efficacy against PCV2d.^7-12 Following PCV2d, PCV2b, then PCV2a are the most prevalent PCV2 genotypes circulating in US herds,¹³ Bandrick said. Research with over 160 known PCV2 strains indicated that a vaccine with two PCV2 genotypes is predicted to provide the broadest coverage available against current and circulating PCV2 viruses,¹⁴ she said. In addition, the vaccine containing two genotypes has better T cell epitope coverage for 746 recent field strains from around the world and reinforces the immune response to those T cell epitopes common across genotypes, providing enhanced depth of coverage.¹⁵ The benefit of this enhanced depth of coverage was shown in a study where vaccines containing two genotypes of PCV2 provided superior protection against infection by either of the two genotypes compared to experimental vaccines containing only one genotype.¹⁶

“Fostera Gold PCV MH has several strong characteristics. It will provide broad genotype coverage, induce a robust cell-mediated response and has a duration of immunity that lasts through the production stage. These attributes provide pork producers with excellent protection against PCV2 disease,” Bandrick said.