A model for the maturation of protective antibody responses to SIV envelope proteins in experimentally immunized monkeys

Cole, Kelly Stefano; Rowles, Jennifer L.; Murphey‐Corb, Michael; Clements, Janice E.; Robinson, James E.; Montelaro, Ronald C.

doi:10.1111/j.1600-0684.1997.tb00319.x

Cited by 14 publications

(14 citation statements)

References 26 publications

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“…Thus, these data indicated a progressive development of protective immunity during the first 6 to 7 months postinfection, suggesting an evolution of virus-specific immune responses to the persistent attenuated EIAV infection. In studies with an attenuated SIV vaccine in monkeys, we have previously reported a protective efficacy of 50% at 3 months postinoculation compared to 100% at 8 months postinoculation (3)(4)(5). Thus, the combined EIAV and SIV attenuated virus vaccine data suggest that the prolonged process for the development of protective vaccine immunity may be a general and distinguishing property of lentiviruses.…”

Section: Discussionmentioning

confidence: 99%

“…Animal lentiviral systems used as AIDS vaccine models have included simian/human immunodeficiency virus (SHIV)-monkey, simian immunodeficiency virus (SIV)-monkey, equine infectious anemia virus (EIAV)-horse, and feline immunodeficiency virus (FIV)-cat models (1). Interestingly, the greatest level of success has been realized with live attenuated animal lentivirus vaccines that are able to drive a critical maturation of virus-specific humoral and cellular immune responses (3,4,15,16,20,29,(36)(37)(38).…”

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confidence: 99%

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Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

Craigo¹,

Feng²,

Steckbeck³

et al. 2005

J Virol

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Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAV UK ⌬S2 derived from a virulent proviral clone, EIAV UK ⌬S2/DU containing a second gene mutation in the virulent proviral clone, and EIAV PR ⌬S2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 10 2 to 10 3 RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAV PV strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

Craigo¹,

Feng²,

Steckbeck³

et al. 2005

J Virol

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“…Although two of the three long-term survivors have neutralizing antibodies against the challenge virus 2.5 years postchallenge, these antibodies were not detected at the time virus replication in the animals was being brought under control. In contrast to the neutralization test, other assays measuring the maturation of the binding antibody responses have suggested a better correlation with protection (8,9,34). It is possible that long-term resistance may be mediated by these kinds of antibodies in combination with memory effector CD8 ϩ T cells and CD4 ϩ T cells modulating the effectors.…”

Section: Cxcr4mentioning

confidence: 99%

A Noninfectious Simian/Human Immunodeficiency Virus DNA Vaccine That Protects Macaques against AIDS

Singh

Liu²,

Sheffer³

et al. 2005

J Virol

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Simian/human immunodeficiency virus SHIV KU2 replicates with extremely high titers in macaques. In order to determine whether the DNA of the viral genome could be used as a vaccine if the DNA were rendered noninfectious, we deleted the reverse transcriptase gene from SHIV KU2 and inserted this DNA (⌬rtSHIV KU2 ) into a plasmid that was then used to test gene expression and immunogenicity. Transfection of Jurkat and human embryonic kidney epithelial (HEK 293) cells with the DNA resulted in production of all of the major viral proteins and their precursors and transient export of a large quantity of the Gag p27 into the supernatant fluid. As expected, no infectious virus was produced in these cultures. Four macaques were injected intradermally with 2 mg of the DNA at 0, 8, and 18 weeks. The animals developed neutralizing antibodies and low enzyme-linked immunospot assay (E-SPOT) titers against SHIV KU2 . These four animals and two unvaccinated control animals were then challenged with heterologous SHIV89.6P administered into their rectums. The two control animals developed viral RNA titers exceeding 10 6 copies/ml of plasma, and these titers were accompanied by the loss of CD4 ؉ T cells by 2 weeks after challenge. The two control animals died at weeks 8 and 16, respectively. All four of the immunized animals became infected with the challenge virus but developed lower titers of viral RNA in plasma than the control animals, and the titers decreased over time in three of the four macaques. The fourth animal remained viremic and died at week 47. Whereas the control animals failed to develop E-SPOT responses, all four of the immunized animals developed anamnestic E-SPOT responses after challenge. The animal that died developed the highest E-SPOT response and was the only one that produced neutralizing antibodies against the challenge virus. These results established that noninfectious DNA of pathogenic SHIV could be used as a vaccine to prevent AIDS, even though the immunological assays used did not predict the manner in which the challenge virus would replicate in the vaccinated animals.

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“…Towards this objective of identifying differences in vaccine immunity in horses with and without detectable infection by challenge virus, we characterized quantitative and qualitative EIAV envelope-specific antibody responses that have previously been used to define the progression from immature non-protective vaccine immunity to mature protective vaccine immunity by attenuated lentiviral vaccines, including EIAV [1,2,39,43]. The results of these comparative serological assays including serum antibody titer, avidity, and conformation revealed a similar characteristic evolution of EIAV envelope-specific antibody responses in protected and unprotected horses during the first six months post inoculation with the EIAV D9 and during the following several months post-infection.…”

Section: Discussionmentioning

confidence: 99%

Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines

Craigo

Durkin

Sturgeon

et al. 2007

Vaccine

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We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV PV ) challenge [1,2]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At two months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy.

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A model for the maturation of protective antibody responses to SIV envelope proteins in experimentally immunized monkeys

Cited by 14 publications

References 26 publications

Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

A Noninfectious Simian/Human Immunodeficiency Virus DNA Vaccine That Protects Macaques against AIDS

Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines

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