Comparison of immune and adverse effects induced by AdjuVac and Freund's complete adjuvant in New Zealand white rabbits (Oryctolagus cuniculus)

Powers, Jenny G.; Nash, Paul B.; Rhyan, Jack C.; Yoder, Christi A.; Miller, Lowell A.

doi:10.1038/laban1007-51

Cited by 26 publications

(25 citation statements)

References 17 publications

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“…However, the use of GnRH vaccines as contraceptive agents in wildlife management has been limited by effective duration, multiple treatments to stimulate adequate antibody response, and deleterious side effects associated with the use of the controversial Freund complete adjuvant (FCA) [4,5]. Recently, an alternative adjuvant (AdjuVac) containing mineral oil and mycobacteria derived from a Johne disease vaccine (Mycopar; Fort Dodge Animal Health, Fort Dodge, IA) has been developed and may be as effective as FCA but is associated with fewer lesions [11].…”

Section: Introductionmentioning

confidence: 99%

Effects of Gonadotropin-Releasing Hormone Immunization on Reproductive Function and Behavior in Captive Female Rocky Mountain Elk (Cervus elaphus nelsoni)1

Powers¹,

Baker²,

Davis³

et al. 2011

Biology of Reproduction

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Fertility control is a potential method for managing overabundant wildlife populations; however, current technology is limited by duration of treatment efficacy and unacceptable side effects. The objective of this study was to determine the efficacy of a single immunization with gonadotropin-releasing hormone (GnRH) vaccine to suppress reproductive function in pregnant female elk and to evaluate potential behavioral and pathological side effects of treatment. Eighteen captive adult female elk were randomly allocated to one of two experimental groups. Ten females were administered a conjugated and adjuvanted GnRH vaccine intramuscularly, and eight elk received an adjuvant sham vaccine without conjugated GnRH. We compared success of existing pregnancy, neonatal survival, subsequent fertility, reproductive behavior rates, and side effects of treatment between January 2006 and January 2010. The GnRH vaccination did not affect existing pregnancy or calf survival during the year that it was applied; however, it reduced the proportion of pregnant females for 3 yr. Male precopulatory behavior rates exhibited toward GnRH-vaccinated females tended to be greater than those directed at sham-vaccinated females during the second half of the breeding season, when GnRH vaccinates continued to be proceptive. Strong immune and inflammatory responses, including robust GnRH antibody concentrations in GnRH vaccinates, and sterile pyogranulomatous injection site abscesses in both groups, were consistent with vaccination. In conclusion, this GnRH vaccine resulted in prolonged, albeit reversible, impairment of fertility, and is associated with extended reproductive behaviors and partial suppression of hypothalamic-pituitary-gonadal axis function in captive female elk.

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Section: Introductionmentioning

confidence: 99%

Effects of Gonadotropin-Releasing Hormone Immunization on Reproductive Function and Behavior in Captive Female Rocky Mountain Elk (Cervus elaphus nelsoni)1

Powers¹,

Baker²,

Davis³

et al. 2011

Biology of Reproduction

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“…The exact mechanism for inducing infertility is not yet certain (Molenaar et al ), but the presence of high anti‐GnRH antibody titers is correlated with infertility in a variety of species (Fagerstone et al ). Numerous GnRH vaccines have been developed and successfully used for decades in physiological research to interrupt the hormonal pathway that controls ovulation (Powers et al ), but their use was not feasible for free‐ranging wildlife because their short duration of action created the need for multiple treatments, and because they contained the controversial Freund's complete adjuvant, which can cause severe injection site reactions (Fagerstone et al , Gray and Cameron ).…”

mentioning

confidence: 99%

Efficacy and health effects of a wildlife immunocontraceptive vaccine on fox squirrels

et al. 2013

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Continued range expansion of introduced eastern fox squirrels (Sciurus niger) in the western United States could lead to widespread damage to agricultural crops, facility infrastructures, and displacement of the native western gray squirrel (S. griseus). Because traditional management alternatives may not be feasible in many areas, public interest in the use of immunocontraceptive to control local populations has increased. We evaluated the efficacy of GonaCon™ immunocontraceptive vaccine for controlling eastern fox squirrel reproduction in Davis, California. We administered GonaCon to 33 male and 26 female fox squirrels, and a control substance to 33 males and 24 females. We subsequently compared the reproductive status, health, and serum concentrations of testosterone and progesterone of our treated and control populations. In our treated population, we also measured serum concentrations of antibodies to gonadotropin‐releasing hormone (GnRH). To determine potential side effects of the vaccine, we recorded body weight and body condition of all animals, examined injection sites during each recapture, and observed the treated squirrels in the field for signs of discomfort and impaired mobility. Over 17 months, none of the recaptured GonaCon‐treated females (n = 20) reproduced, compared to 12 of 15 control females. Treated males and females developed sufficient antibodies to GnRH to suppress reproduction, suggesting that GonaCon has the potential to be 100% effective in inhibiting reproduction in both sexes. We also observed a reduction in physical signs of reproductive activity for males (P < 0.001) and in hormone levels of both females (P < 0.001) and males (P < 0.001). Control and GonaCon‐treated animals did not differ in body weight but vaccinated squirrels had poorer body condition scores and exhibited severe injection site abscesses. The abscesses may have been caused by the GnRH conjugate used in GonaCon. In our study, GonaCon was effective in reducing eastern fox squirrel reproduction. Changes in the conjugate or its preparation may reduce the severity of associated injection site reactions. © 2013 The Wildlife Society

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“…It has long been suggested that the granuloma formed at the injection site when using mineral oil is related to the fact the mineral oil cannot be metabolized by the animal. Powers et al (2007) attempted to answer this question by comparing vaccines made of mineral oil as compared to vegetable oil (squalene). They found that there was little difference in the injection site reaction between the two forms of oil.…”

Section: Mineral Oil Vs Vegetable Oil (Squalene)mentioning

confidence: 99%

“…It is known that killed bacteria in the adjuvant have increased the injection site reaction (Powers et al 2007). We have decreased the amount of killed bacteria in the AdjuVac ™ adjuvant to reduce its negative effect.…”

Section: Avium-free Water-soluble Adjuvantsmentioning

confidence: 99%

Immune Mechanisms and Characterization of Injection Site Reactions Involved in the Multi-Year Contraceptive Effect of the GonaCon™ Vaccine

Miller¹,

Fagerstone²,

Kemp³

et al. 2008

vertebrate_pest_conference

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The term "vaccine" has traditionally been associated with establishing immunity (antibodies) to a disease. This immunity is usually developed following administration of killed microorganisms. Disease vaccines typically require 1 to 3 injections, depending on the antigen design and efficacy of the vaccine. The effectiveness of the disease vaccine depends on the immune response developed by the host following exposure to the disease organism. The immunocontraceptive vaccine GonaCon ™ is designed to produce immunity to the "self" hormone (GnRH), which is essential to reproductive activity in the mammal. Antibodies to GnRH reduce its biological activity resulting in infertility of both sexes. GonaCon ™ 's effectiveness as a single-injection immunocontraceptive wildlife vaccine depends on 4 factors. The first is the use of a large foreign mollusk protein in the GnRH conjugate. Second is the design of mollusk/GnRH protein conjugate that presents the GnRH antigen in a repetitious fashion. This design mimics the "danger signal" found in bacterial pathogens to which the animal has been previously exposed. Third is the addition to the vaccine of micrograms of Mycobacterium avium, which is ubiquitous in the environment and activates memory cells. The fourth factor is use of a water-in-oil emulsion, which provides a depot at the injection site, allowing a slow release of the vaccine. With this formulation, the vaccine is presented to the body as a "chronic infection", even though it is not infectious. The granuloma that normally develops at the injection site plays a prime role in the host's defense against this "chronic infection". A WHO report on the use of the alum adjuvant in human vaccines states that "development of a small granuloma is inevitable with vaccines adjuvanted with aluminum, and is to be considered necessary to the efficacy of the adjuvant." Researching GonaCon ™ for use in companion animals, NWRC has looked at many different adjuvants intended to reduce the injection site reaction while at the same time retaining an effective vaccine. This paper reports on the role of the adjuvant and the injection site on the effectiveness of the vaccine.

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Comparison of immune and adverse effects induced by AdjuVac and Freund's complete adjuvant in New Zealand white rabbits (Oryctolagus cuniculus)

Cited by 26 publications

References 17 publications

Effects of Gonadotropin-Releasing Hormone Immunization on Reproductive Function and Behavior in Captive Female Rocky Mountain Elk (Cervus elaphus nelsoni)1

Effects of Gonadotropin-Releasing Hormone Immunization on Reproductive Function and Behavior in Captive Female Rocky Mountain Elk (Cervus elaphus nelsoni)1

Efficacy and health effects of a wildlife immunocontraceptive vaccine on fox squirrels

Immune Mechanisms and Characterization of Injection Site Reactions Involved in the Multi-Year Contraceptive Effect of the GonaCon™ Vaccine

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