Rabies-Specific Antibodies: Measuring Surrogates of Protection against a Fatal Disease

Moore, Susan M.; Hanlon, Cathleen A.

doi:10.1371/journal.pntd.0000595

Cited by 150 publications

(112 citation statements)

References 29 publications

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“…However, vaccination costs against rabies virus can be highly prohibitive and severely limit the usage of this life-saving vaccine. Intradermal regimes of vaccinations have been developed and used in tropical countries in an effort to reduce vaccination costs [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Even though this new vaccination mode may reduce costs, it requires multiple visits to vaccination facilities and skilled practitioners in order to administer the vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, IMT504 has been demonstrated to be immunostimulatory only in rats, monkeys and humans, with IMT504 being most active in humans [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Therefore, we decided to perform a pilot study of rabies vaccination in human volunteers.…”

Section: Discussionmentioning

confidence: 99%

“…Titers of anti-rabies glycoprotein antibodies have been reported to have a reasonable correlation with the titers of serum neutralizing antibodies measured by the rapid fluorescent focus inhibition test (RFFIT), which is currently accepted as the gold standard technique [13][14][15]. Table 1 shows that after the second injection, all of the individuals in the IMT504 group reached protective levels (>0.5 IU/ml) as defined by the WHO [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Notably, four out of five reached levels 60 -90 times higher than the required protective level after the third dose.…”

Section: Immunization Of Human Volunteers With Vero Cell Rabies Vaccimentioning

confidence: 99%

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IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

Montaner¹,

Nichilo²,

Rodríguez³

et al. 2012

WJV

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Background: Rabies virus infection causes encephalitis, which is almost always fatal. Vaccination can be extremely effective at preventing disease but is prohibitively costly. Vaccine formulations allowing dose-sparing and fewer inoculations with faster antibody response would be extremely desirable. IMT504, an immunostimulatory non-CpG oligodeoxynucleotide, is a highly potent vaccine adjuvant. Methods: Human and rat antibody measurements, and rat challenge studies were performed. Results: In rats, highly effective immune responses with IMT504 were observed even after diluting vaccine up to 1/625. In highly lethal, live intracerebral rabies challenge studies, protection occurred even with extremely dilute vaccine plus IMT504. In humans, antibody titers developed faster and were significantly higher with IMT504-adjuvanted diluted vaccine vs non-adjuvanted vaccine (full strength or diluted). All five administered IMT504-adjuvanted diluted vaccine reached protective antibodies (≥0.5 IU/ml) after the second injection. After the third injection, individuals receiving IMT504-adjuvanted diluted vaccine reached levels approximately 10 times higher than controls (M ± SEM: 31.0 ± 10.9 vs 3.40 ± 0.99 IU/ml). Conclusions: These data suggest that IMT504 may allow fewer inoculations, highly significant dose-sparing of vaccine, rapid antibody production and protection from rabies. Extensive clinical studies are necessary to confirm if the use of IMT504 will permit significantly greater access to highly effective life-saving rabies vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Immunization Of Human Volunteers With Vero Cell Rabies Vaccimentioning

confidence: 99%

See 1 more Smart Citation

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

Montaner¹,

Nichilo²,

Rodríguez³

et al. 2012

WJV

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“…So WHO and many countries drug agency suggest the method of rapid and reproducible in vitro the availability of alternatives, this method remains the standard method for measuring rabies-specific antibodies [21]. The RFFIT method spend only 2 days, and can detect a large number of samples once time, and do not require the use of animals (3R principles of experimental animals), WHO strongly recommended the method, RFFIT method has been the approved by the agency of drug regulatory of China for the potency detection of anti-rabies serum/immunoglobulin now [22].…”

Section: Seroconversion Of Tcalrv-bmentioning

confidence: 99%

Formulation, Efficacy and Immunogenicity Studies of a Liquid State Rabies Vaccine with Magnesium Chloride as Stabilizer

Selvaraj¹,

Rajendran²

2015

J Vaccines Vaccin

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Propagation of fixed rabies virus strain in vero cell line, ultra filtration of rabies viral harvest, betapropiolactone inactivation subsequent purification, total protein nitrogen quantification, Rapid Fluorescent focus inhibition test, MgCl 2 based liquid rabies vaccine formulation (TCALRV-B) and immune response analysis. The vero cell derived PV 11 rabies viral titers were found that 10 -5.3 , ultra filtrated, betapropiolactone inactivated and viral protein qualities were within the range (WHO). The total protein concentration and PN 2 was 577.6, 0.26 mg/ml respectively. The host cellular protein and residual cellular DNA was 16 ng/single human doses and below 100 pg/ml respectively it reveals within the limit. The RFFIT titer of the TCALRV-B possessed higher immune response (8 IU/ml) of rabies neutralizing antibodies on 14 th on 21 st day the titer was four fold increasing even after 90 th day it reveals its immunopotency. The TCALRV-B contained all the quality attributes to fulfill the regulatories although it contained potency, immunogenicity and safety as in vivo study shows lesser immunogenic during the booster doses. This may be due to the unadsorption of rabies viral proteins by MgCl 2 as adjuvant.

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“…The RFFIT is currently the gold standard and reference technique for most laboratories. [5][6][7] An RVNA titer of ≥ 0.5 U/mL is globally recognized as the threshold of seroconversion for humans. 7 Values reported in this manner (U/mL) are titers expressed as standard units.…”

mentioning

confidence: 99%

Duration of serum antibody response to rabies vaccination in horses

Harvey¹,

Watson²,

Brault³

et al. 2016

javma

Self Cite

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OBJECTIVETo investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses. DESIGN Serologic response evaluation.ANIMALS 48 horses with an undocumented vaccination history. PROCEDURESHorses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus-neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the basis of World Health Organization recommendations for humans. Values were compared between horses < 20 and ≥ 20 years of age and between horses inferred to have been previously vaccinated and those inferred to be immunologically naïve. RESULTSA protective RVNA value (≥ 0.5 U/mL) was maintained for 2 to 3 years in horses inferred to have been previously vaccinated on the basis of prevaccination RVNA values. No significant difference was evident in response to rabies vaccination or duration of protective RVNA values between horses < 20 and ≥ 20 years of age. Seven horses were poor responders to vaccination. Significant differences were identified between horses inferred to have been previously vaccinated and horses inferred to be naïve prior to the study. CONCLUSIONS AND CLINICAL RELEVANCEA rabies vaccination interval > 1 year may be appropriate for previously vaccinated horses but not for horses vaccinated only once. Additional research is required to confirm this finding and characterize the optimal primary dose series for rabies vaccination. (J Am Vet Med Asssoc 2016;249:xxx-xxx) revaccination is currently recommended by vaccine manufacturers and in the vaccination guidelines of the AAEP. 3 Research in several animal species indicates that the primary correlate of protection against rabies is the presence of neutralizing antibody in serum. 4 The humoral immune response to rabies vaccination can be evaluated with the RFFIT or fluorescent antibody virus neutralization test, both of which are used for in vitro measurement of RVNA concentration in serum samples. The RFFIT is currently the gold standard and reference technique for most laboratories. [5][6][7] An RVNA titer of ≥ 0.5 U/mL is globally recognized as the threshold of seroconversion for humans. 7 Values reported in this manner (U/mL) are titers expressed as standard units. This value of 0.5 U/mL, when obtained via RFFIT or fluorescent antibody virus neutralization, is also recognized by regulatory authorities in most rabies-free areas as proof of adequate response to vaccination for importation of cats and dogs. 5 No general consensus currently exists regarding the RVNA titer needed to confer protection

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Rabies-Specific Antibodies: Measuring Surrogates of Protection against a Fatal Disease

Cited by 150 publications

References 29 publications

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

Formulation, Efficacy and Immunogenicity Studies of a Liquid State Rabies Vaccine with Magnesium Chloride as Stabilizer

Duration of serum antibody response to rabies vaccination in horses

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