Diva strategy in animal disease control and eradication: a review

Conventional vaccines are important for controlling infectious diseases in livestock but have a major limitation, they cannot differentiate between animals that are vaccinated and those that are naturally infected. This diagnostic gap complicates disease monitoring, slows down eradication programs, and disrupts international trade. To address this challenge, the concept of DIVA (Differentiating Infected from Vaccinated Animals), also referred to as marker vaccination, was introduced by Van Oirschot in 1999. DIVA vaccines are specially designed either by removing certain antigens (negative markers) or by adding foreign antigens (positive markers), creating a unique immunological signature in vaccinated animals that can be distinguished from the immune response in naturally infected animals. When used in combination with specific companion diagnostic tests such as ELISA, this strategy enables clear identification of infected animals within vaccinated populations. This review describes the fundamental principles, types, and mechanisms of DIVA vaccines including deletion mutants, subunit vaccines, live attenuated, inactivated, recombinant, and DNA/vector based platforms and their applications in controlling major diseases such as Pseudorabies, Foot and Mouth Disease, Infectious Bovine Rhinotracheitis, Classical Swine Fever, Avian Influenza, Lumpy Skin Disease, Brucellosis, and Rabies. The review also highlights the benefits of DIVA in supporting disease control and trade facilitation, discusses current limitations, and outlines future prospects for advancing this strategy in global veterinary medicine.