Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance. (Article)

1996-01-01T00:00:00Z

Commercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and nucleoprotein (NP) contents were determined in an antigen competition ELISA. The GP content proved to correlate well with the potency found in the mouse potency test (r = 0.95, p < 0.01), whereas no such correlation was found for the NP content (r approximately 0, p > 0.05). After the manufacturers were told about the results, one of the two vaccines that did not comply with the requirements was withdrawn from the market. Measurement of the GP content of a second lot of the remaining vaccines indicated that sufficiently high levels of GP were present in all five. Additional in vivo testing in mice for efficacy against intracerebral challenge with the Dutch bat rabies virus EBL1-12 resulted in acceptable levels of protection with four of these five vaccines of the second lot. The data presented illustrate the need for continued potency evaluation of veterinary rabies vaccines in the Netherlands.

Modulation of antiviral immune responses by exogenous cytokines: effects of tumour necrosis factor-α interleukin-1 α, interleukin-2 and interferon-γ on the immunogenicity of an inactivated rabies vaccine. (Article)

1994-01-01T00:00:00Z

In vivo administration of exogenous cytokines may influence elicited immune responses, and hence may change the efficacy of a vaccine. We investigated the effects of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) on the immune response elicited by inactivated rabies virus vaccine in a mouse model. Each of the cytokines increased virus-specific IgG responses after primary and after secondary immunization. A single dose of 1.3 ng TNF-alpha or IL-1 alpha, when injected shortly before vaccination, only marginally stimulated resistance to challenge infection (four- and seven-fold, respectively) without enhancing virus neutralizing antibody (VNAb) responses. In contrast, a single injection of 10(3) units of IFN-gamma or five daily injections of 1.6 micrograms IL-2 increased vaccine dilutions protecting 50% of mice (PD50 values) 77- to 50-fold, respectively, with a concomitant enhancement of VNAb. At a 1:10,000 dilution of a standard inactivated rabies vaccine preparation both IFN-gamma and IL-2 increased protective immunity without enhancing VNAb responses; in non-vaccinated animals this treatment had no effect on resistance to challenge. Combined administration of IFN-gamma and IL-2 synergistically enhanced VNAb responses. In contrast to the other cytokines tested, IFN-gamma preferentially stimulated virus-specific IgG2a production. It also augmented the vaccine-induced priming of rabies virus-specific splenocyte proliferation. These results document that certain cytokines alone or in combination are potent immunological adjuvants which may direct and modulate immunization-induced antiviral immune responses.

Vermeulen, A.A.

Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance. (Article)

Modulation of antiviral immune responses by exogenous cytokines: effects of tumour necrosis factor-α interleukin-1 α, interleukin-2 and interferon-γ on the immunogenicity of an inactivated rabies vaccine. (Article)