Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Virology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Vaccines and Antiviral Agents

Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques

Ilnour Ourmanov, Miroslawa Bilska, Vanessa M. Hirsch, David C. Montefiori
Ilnour Ourmanov
Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miroslawa Bilska
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vanessa M. Hirsch
Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David C. Montefiori
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JVI.74.6.2960-2965.2000
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene products (MVA-SIV). Animals received either MVA-gag-pol, MVA-env, MVA-gag-pol-env, or nonrecombinant MVA. Although no animals were completely protected from infection with SIV, animals immunized with recombinant MVA-SIV vaccines had lower virus loads and prolonged survival relative to control animals that received nonrecombinant MVA (I. Ourmanov et al., J. Virol. 74:2740–2751, 2000). Titers of neutralizing antibodies measured with the vaccine strain SIVsmH-4 were low in the MVA-env and MVA-gag-pol-env groups of animals and were undetectable in the MVA-gag-pol and nonrecombinant MVA groups of animals on the day of challenge (4 weeks after final immunization). Titers of SIVsmH-4-neutralizing antibodies remained unchanged 1 week later but increased approximately 100-fold 2 weeks postchallenge in the MVA-env and MVA-gag-pol-env groups while the titers remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups. This anamnestic neutralizing antibody response was also detected with T-cell-line-adapted stocks of SIVmac251 and SIV/DeltaB670 but not with SIVmac239, as this latter virus resisted neutralization. Most animals in each group had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge. Titers of neutralizing antibodies were low or undetectable until about 12 weeks of infection in all groups of animals and showed little or no evidence of an anamnestic response when measured with SIVsmE660. The results indicate that recombinant MVA is a promising vector to use to prime for an anamnestic neutralizing antibody response following infection with primate lentiviruses that cause AIDS. However, the Env component of the present vaccine needs improvement in order to target a broad spectrum of viral variants, including those that resemble primary isolates.

Efforts to develop an AIDS vaccine have included the use of recombinant poxvirus vectors that are engineered to express one or more gene products of human immunodeficiency virus type 1 (HIV-1) (12, 15, 27). Vectors such as these have the potential to generate virus-specific CD8+ cytotoxic T lymphocytes (CTL) and neutralizing antibodies (7) as two immune responses considered important for HIV-1 vaccine efficacy (14). Studies in macaques have shown that recombinant vaccinia virus vectors containing the Env glycoproteins of simian immunodeficiency virus (SIV) prime B cells to produce low levels of SIV-specific neutralizing antibodies and that subsequent boosting with subunit protein can dramatically elevate the levels of those antibodies (20, 21). A similar priming and boosting effect for neutralizing antibody production has been observed in phase I clinical trials of candidate HIV-1 vaccines consisting of recombinant vaccinia or canarypox virus vectors followed by Env glycoprotein inoculation (1, 5, 6, 41). These results suggest that recombinant poxviruses might prime for a similar secondary (anamnestic) neutralizing antibody response following virus infection. Hu et al. showed that a recombinant vaccinia virus vector containing HIV-1 gp160 (strain LAV) primed for anamnestic neutralizing antibody production in chimpanzees following challenge with homologous virus (22). Although it is currently unknown whether an accelerated neutralizing antibody response would provide a clinical benefit in HIV-1-infected individuals, the fact that many months are needed for neutralizing antibodies to rise to detectable levels following initial infection (24, 34, 40, 42) leaves open the possibility that it will.

We sought to determine whether prior inoculation with a recombinant attenuated poxvirus known as modified vaccinia virus Ankara (MVA) and containing the Env glycoproteins of SIV would prime B cells for an anamnestic neutralizing antibody response in rhesus macaques (Macaca mulatta) after intravenous challenge with pathogenic SIVsmE660 in cases where complete protection was not achieved. Four groups of six macaques received four inoculations intramuscularly with 108 PFU of either MVA, MVA-gag-pol, MVA-env, or MVA-gag-pol-env. Each of these poxvirus vectors has been described previously (17, 39, 45) and contained SIV components derived from nonpathogenic, molecularly cloned SIVsmH-4 (18). The animals were challenged intravenously with the related uncloned, highly pathogenic SIVsmE660 (19, 23) 4 weeks after final boosting. Although all animals became infected, those that received MVA-gag-pol, MVA-env, and MVA-gag-pol-env had lower plasma viral RNA (P = 0.0016) and prolonged survival relative to animals that received nonrecombinant MVA (39). There were no significant differences in the levels of plasma viremia between the three groups of animals receiving recombinant MVAs. Plasma samples were obtained prior to vaccination, on the day of challenge, and at multiple times for up to 28 weeks postchallenge. Neutralizing activity against SIV was assessed in a CEMx174-cell-killing assay as described previously (32). Unless indicated otherwise, virus stocks were produced in either H9 cells (SIVsmH-4, SIVmac251, and SIV/DeltaB670), CEMx174 cells (SIVsmE660), or rhesus peripheral blood mononuclear cells (PBMC) (SIVmac239). An exception was one set of neutralization assays that was performed with the original animal challenge stock of SIVsmE660 grown in rhesus PBMC.

Neutralizing antibodies were first assessed with the vaccine strain of the virus, SIVsmH-4. The results are shown in Fig.1. No SIVsmH-4-neutralizing antibodies were detected on the day of challenge in animals that received nonrecombinant MVA or MVA-gag-pol, which is consistent with the absence of env in these vaccines. Low titers of SIVsmH-4-neutralizing antibodies were detected on the day of challenge in three recipients of MVA-env (titers of 86 to 663) and four recipients of MVA-gag-pol-env (titers of 85 to 274). The titers remained essentially unchanged 1 week later for all animals. Titers of SIVsmH-4-neutralizing antibodies increased dramatically 2 weeks postchallenge in the MVA-env (average titer, 39,848) and MVA-gag-pol-env (average titer, 25,160) and remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups at this time. These results suggest that MVA-env and MVA-gag-pol-env primed B cells sufficiently to permit a rapid and dramatic anamnestic neutralizing antibody response between 1 and 2 weeks postchallenge. A similar anamnestic antibody response was detected by SIVsmH-4 gp130 enzyme-linked immunosorbent assay (39). Nearly all animals had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge (Fig. 1). Exceptions at 8 weeks were two animals in the nonrecombinant MVA group, whose neutralization titers were extremely low (animals D3 and D6). These two animals progressed to AIDS very rapidly (39). Early onset of virus-induced immune suppression in the two rapid progressors could account for their poor antibody-neutralizing response.

Fig. 1.
  • Open in new tab
  • Download powerpoint
Fig. 1.

Time course of SIVsmH-4-neutralizing antibody production following intravenous inoculation of vaccinated macaques with SIVsmE660. SIVsmH-4-neutralizing antibodies were measured in plasma samples obtained on the day of challenge and at multiple time points for 12 weeks postchallenge. Titers of neutralizing antibodies are the reciprocal plasma dilution at which 50% of CEMx174 cells were protected from virus-induced cell killing. Undetectable neutralization was given a value of 30, which was the lowest reciprocal plasma dilution tested. Panel A, MVA-gag-pol; panel B, MVA-env; panel C, MVA-gag-pol-env; panel D, MVA. †, animals sacrificed because of clinical manifestations of AIDS; ✞, animal that died of causes unrelated to AIDS.

Neutralizing antibodies were next assessed with SIVsmE660. This virus is an uncloned quasispecies of the same parental strain from which SIVsmH-4 was derived (18) and, therefore, is closely related to SIVsmH-4 genetically. As shown in Fig.2, all animals were negative for SIVsmE660-neutralizing antibodies on the day of challenge. Also, no neutralization of this virus was detected 2 weeks postchallenge, and little neutralization was detected 8 weeks postchallenge despite the fact that most animals had very high SIVsmH-4 neutralization titers at one or both of these time points. It is important to note that preferential neutralization of SIVsmH-4 by week-8 plasma samples was seen for all groups of animals, including those that received recombinant MVAs lacking Env (i.e., MVA-gag-pol and nonrecombinant MVA). This outcome indicates that the inability to neutralize SIVsmE660 was not related to vaccine-induced immune interference associated with SIVsmH-4 Env priming (38). The outcome is more likely explained by epitopes shared by both viruses that, although they are highly immunogenic in infected macaques, are not adequately exposed for antibody binding on the native SIVsmE660 Env complex relative to their exposure on the native SIVsmH-4 Env complex. On the basis of immunophenotype and implied differences in native envelope glycoprotein structure, SIVsmH-4 resembles a T-cell-line-adapted (TCLA) strain, whereas SIVsmE660 resembles primary isolates of HIV-1 (3, 35, 49).

Fig. 2.
  • Open in new tab
  • Download powerpoint
Fig. 2.

Time course of challenge-strain-neutralizing antibody production following intravenous inoculation of vaccinated macaques with SIVsmE660. SIVsmE660-neutralizing antibodies were measured in plasma samples obtained on the day of challenge and at multiple time points for 28 weeks postchallenge. Titers of neutralizing antibodies are the reciprocal plasma dilution at which 50% of CEMx174 cells were protected from virus-induced cell killing. Undetectable neutralization was given a value of 30, which was the lowest reciprocal plasma dilution tested. Panel A, MVA-gag-pol; panel B, MVA-env; panel C, MVA-gag-pol-env; panel D, MVA. †, animals sacrificed because of clinical manifestations of AIDS; ✞, animal that died of causes unrelated to AIDS.

Neutralization of SIVsmE660 was first detected 12 weeks postchallenge with plasmas from a subset of animals in each group, where the titers either peaked at this time or continued to rise for at least 20 to 28 weeks. Peak titers of SIVsmE660-neutralizing antibodies never reached the levels observed with SIVsmH-4 and, in fact, were always >10-fold lower in magnitude, again indicating that SIVsmE660 is much less sensitive to antibody-mediated neutralization than SIVsmH-4. It should be noted that the rapid progressors in the MVA group that developed low levels of neutralizing antibody to SIVsmH-4 also produced no antibodies that neutralized SIVsmE660.

The difficulty by which SIVsmE660 was neutralized relative to SIVsmH-4 suggests that detection of an anamnestic neutralizing antibody response targeting SIVsmE660 would be delayed relative to the response measured with SIVsmH-4. The MVA-gag-pol-env group of animals was the only case where an anamnestic neutralizing antibody response might have been detected with SIVsmE660. For example, two of six animals in this group had low titers of SIVsmE660-neutralizing antibodies 8 weeks postchallenge. By comparison, all animals in the remaining groups were negative (<30) at this time. In addition, five of six animals in the MVA-gag-pol-env group had titers of SIVsmE660-neutralizing antibodies that surpassed those in the MVA-gag-pol and MVA-env groups of animals 12 weeks postchallenge. However, because the magnitude of neutralization in the MVA-gag-pol-env animals was not much different from the nonrecombinant MVA group, any anamnestic response targeting SIVsmE660 was probably weak.

We next examined whether an anamnestic neutralizing antibody response could be detected with other strains of SIV. For this, plasma samples from three animals in each group were assessed for their ability to neutralize highly neutralization-sensitive, TCLA stocks of SIV/DeltaB670 (50) and SIVmac251 (25, 30), and a neutralization-insensitive stock of molecularly cloned SIVmac239/nef-open (30, 32). Because the anamnestic responses detected with SIVsmH-4 were fairly uniform, we selected plasma samples randomly from a subset of animals in each group for these assessments. The results shown in Tables1 and 2include titers measured with SIVsmH-4 and SIVsmE660 derived from Fig. 1and 2 for comparison. Table 1 shows that an anamnestic neutralizing antibody response was detectable with SIV/DeltaB670 and, to a lesser extent, with SIVmac251 2 weeks postchallenge in the MVA-envand MVA-gag-pol-env groups of animals. Table 2 shows that the anamnestic response was no longer evident 8 weeks postchallenge, which was similar to the results obtained with SIVsmH-4. Table 2 also shows that all 8-week plasma samples failed to neutralize SIVmac239. We conclude that the neutralizing activity of the antibodies produced during the anamnestic phase, and shortly thereafter, were highly specific for SIVsmH-4 and heterologous TCLA strains of SIV.

View this table:
  • View inline
  • View popup
Table 1.

Magnitude and cross-reactivity of neutralizing antibodies detected 2 weeks post-virus challenge

View this table:
  • View inline
  • View popup
Table 2.

Magnitude and cross-reactivity of neutralizing antibodies detected 8 weeks post-virus challenge

The fact that passively administered neutralizing antibodies have proven effective against AIDS viruses in macaques (4, 8, 13, 28, 33, 46) and hu-PBL-SCID mice (9) suggests that neutralizing antibody induction would benefit an HIV-1 vaccine. How much of a benefit the antibodies provide may depend on their ability to neutralize diverse genetic variants of the virus, including primary isolates (9, 33, 46). Antibodies produced during the anamnestic phase in our vaccinated animals did not neutralize SIVsmE660, making it uncertain that the antibodies contributed to the partial efficacy observed (39). The fact that equal levels of efficacy were achieved regardless of whether env was present in the recombinant MVA vaccine (39) is further evidence that neutralizing antibodies probably contributed little. Nonetheless, it was possible that our assay stock of SIVsmE660 produced in CEMx174 cells was less sensitive to neutralization than the animal challenge stock produced in rhesus PBMC and, therefore, underestimated neutralization potency. To address this possibility, we performed neutralization assays with the animal challenge stock of SIVsmE660 without further passage. Because this stock was limited in supply and is valuable for animal challenges, our assessments were made on a subset of plasma samples. We selected five samples obtained during the anamnestic phase (2 weeks postchallenge) that contained high titers of SIVsmH-4-neutralizing antibodies (animals B1, B5, B6, C1, and C3), and three samples obtained 28 weeks postchallenge that neutralized our assay stock of SIVsmE660. As can be seen in Table3, titers of neutralizing antibodies obtained with the 28-week-postchallenge samples were similar for both stocks of virus in two of three cases. Also, we showed that 50% protection from virus-induced cell killing corresponds very closely to a 90% reduction in p27 Gag antigen synthesis in these assays (Table3). Although the titer was approximately 4 times higher with the animal challenge stock in one case (animal B6), we do not consider this to be a major difference with respect to occasional assay-to-assay variation. No neutralization of the challenge stock of SIVsmE660 was detected with plasmas obtained during the anamnestic phase, which agreed with results obtained with our assay stock of the virus.

View this table:
  • View inline
  • View popup
Table 3.

Comparative neutralization of the assay and animal challenge stocks of SIVsmE660

We conclude that SIVsmH-4 Env did not prime for a secondary neutralizing antibody response to SIVsmE660 in these studies. However, there are a number of cases where antibodies lacking detectable neutralizing activity in vitro were nonetheless capable of preventing infection by other viruses (10, 26, 29, 36, 37, 43, 44), and at least one example exists in the SIV-macaque model (48). With this in mind, we do not wish to exclude the possibility that nonneutralizing antibodies, particularly those involved in antibody-dependent cytotoxicity (47) and immune complex clearance (31), played a role in our studies.

The ability to prime for a more-broadly cross-reactive neutralizing antibody response with this vaccine candidate will most likely depend on the nature of the immunogen(s) incorporated into the vector. One example would be to use multiple recombinant MVA vectors, each containing the Env glycoproteins from a different strain of virus as a single vaccination modality. An alternate strategy would be to incorporate the Env glycoproteins from a single strain of virus after modifying them to present conserved neutralization epitopes in a highly immunogenic configuration. An important first step will be to determine whether greater efficacy can be achieved in the present model by priming for a neutralizing antibody response that is capable of targeting the challenge virus. This can be tested by incorporating the Env glycoproteins from a strain of virus that is closely matched to the challenge virus in terms of antigenicity and quasispecies complexity. We are in the process of pursuing this goal by using the highly pathogenic, molecularly cloned SIVsmE543-3 as both the vaccine and challenge strain. This virus exhibits a neutralization-resistant phenotype reminiscent of primary HIV-1 isolates (16).

With the majority of HIV-1 transmissions occurring in developing countries that have limited financial resources, the high cost of Env glycoprotein production, especially in the case of a polyvalent vaccine, will be a major economic challenge for global immunization (2). Recombinant vectors offer a cost-effective and feasible alternative. Although inoculation with recombinant poxviruses without Env glycoprotein boosting has not induced high levels of neutralizing antibodies, efficient B-cell priming by these vectors should facilitate an anamnestic neutralizing antibody response to infection. An appropriate anamnestic B-cell response might exert sufficient pressure on the virus during early stages of infection as the CTL response matures. One of the vectors used here (MVA-gag-pol) was previously shown to elicit potent SIV-specific CTL in macaques (45). Together, these immune responses might be capable of controlling virus replication to an extent that would limit immune suppression and virus transmission better than either response alone.

ACKNOWLEDGMENTS

We thank Ronald C. Desrosiers for providing SIVmac251 and SIVmac239 and Michael Murphy-Corb for providing SIV/DeltaB670.

Partial support for these studies was provided by a grant from the NIH (AI-85343).

FOOTNOTES

    • Received 31 August 1999.
    • Accepted 23 December 1999.
  • Copyright © 2000 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Belshe R. B.,
    2. Gorse G. J.,
    3. Mulligan M. J.,
    4. Evans T. G.,
    5. Keefer M. C.,
    6. Excler J.-L.,
    7. Duliege A.-M.,
    8. Tartaglia J.,
    9. McNamara J.,
    10. Kai-Lin H.,
    11. Montefiori D.,
    12. Weinhold K.
    Rapid induction of HIV-1 immune responses by canarypox (ALVAC) HIV-1 and gp120 SF2 recombinant vaccines in uninfected volunteers.AIDS 12 1998 2407 2415
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Bloom B. R.
    The highest attainable standard: ethical issues in AIDS vaccines.Science 279 1998 186 188
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Burton D. R.,
    2. Montefiori D. C.
    The antibody response in HIV-1 infection.AIDS 11 (Suppl. A) 1997 S87 S98
    OpenUrl
  4. 4.↵
    1. Clements J. E.,
    2. Montelaro R. C.,
    3. Zink M. C.,
    4. Amedee A. M.,
    5. Miller S.,
    6. Trichel A. M.,
    7. Jagerski B.,
    8. Hauer D.,
    9. Martin L. N.,
    10. Bohm R. P.,
    11. Murphey-Corb M.
    Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus.J. Virol. 69 1995 2737 2744
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Clements-Mann M. L.,
    2. Weinhold K.,
    3. Matthews T. J.,
    4. Graham B. S.,
    5. Gorse G. J.,
    6. Keefer M. C.,
    7. McElrath M. J.,
    8. Hsieh R. H.,
    9. Mestecky J.,
    10. Zolla-Pazner S.,
    11. Mascola J.,
    12. Scwartz D.,
    13. Silicano R.,
    14. Corey L.,
    15. Wright P. F.,
    16. Belshe R.,
    17. Dolin R.,
    18. Jackson S.,
    19. Xu S.,
    20. Fast P.,
    21. Walker M. C.,
    22. Stablein D.,
    23. Excler J.-L.,
    24. Tartaglia J.,
    25. Duliege A. M.,
    26. Sinangil F.,
    27. Paoletti E.
    Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults.J. Infect. Dis. 177 1998 1230 1246
    OpenUrlCrossRefPubMedWeb of Science
  6. 6.↵
    1. Cooney E. L.,
    2. McElrath M. J.,
    3. Corey L.,
    4. Hu S.-L.,
    5. Collier A. C.,
    6. Arditti D.,
    7. Hoffman M.,
    8. Coombs R. W.,
    9. Smith G. E.,
    10. Greenberg P. D.
    Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regimen consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein.Proc. Natl. Acad. Sci. USA 90 1993 1882 1886
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Excler J.-L.,
    2. Plotkin S.
    The prime-boost concept applied to HIV preventive vaccines.AIDS 11 (Suppl. A) 1997 S127 S137
    OpenUrl
  8. 8.↵
    1. Foresman L.,
    2. Jia F.,
    3. Li Z.,
    4. Wang C.,
    5. Stephens E. B.,
    6. Sahni M.,
    7. Narayan O.,
    8. Joag S. V.
    Neutralizing antibodies administered before, but not after, virulent SHIV prevent infection in macaques.AIDS Res. Hum. Retrovir. 14 1998 1035 1043
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    1. Gauduin M.-C.,
    2. Parren P. W. H. I.,
    3. Weir R.,
    4. Barbas C. F.,
    5. Burton D. R.,
    6. Koup R. A.
    Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1.Nat. Med. 3 1997 1389 1393
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Gould E. A.,
    2. Buckley A.,
    3. Barret A. D. T.,
    4. Cammack N.
    Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non-structural yellow fever virus proteins confer immunity in mice.J. Gen. Virol. 67 1986 591 595
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.
    1. Graham B. S.,
    2. Matthews T. J.,
    3. Belshe R. B.,
    4. Clements M. L.,
    5. Dolin R.,
    6. Wright P. F.,
    7. Gorse G. J.,
    8. Schwartz D. H.,
    9. Keefer M. C.,
    10. Bolognesi D. P.,
    11. Corey L.,
    12. Stablein D. M.,
    13. Esterlitz J. R.,
    14. Hu S.-L.,
    15. Smith G. E.,
    16. Fast P. E.,
    17. Koff W. C.
    Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naı̈ve adults.J. Infect. Dis. 167 1993 533 537
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    1. Graham B. S.,
    2. Wright P. F.
    Candidate AIDS vaccines.J. Engl. J. Med. 333 1995 1331 1339
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    1. Haigwood N. L.,
    2. Watson A.,
    3. Sutton W. F.,
    4. McClure J.,
    5. Lewis A.,
    6. Ranchalis J.,
    7. Travis B.,
    8. Voss G.,
    9. Letvin N. L.,
    10. Hu S.-L.,
    11. Hirsch V. M.,
    12. Johnson P. R.
    Passive immune globulin therapy in the SIV/macaque model: early intervention can alter disease profile.Immunol. Lett. 51 1996 107 114
    OpenUrlCrossRefPubMedWeb of Science
  14. 14.↵
    1. Haynes B. F.,
    2. Pantaleo G.,
    3. Fauci A. S.
    Toward an understanding of the correlates of protective immunity to HIV infection.Science 271 1996 324 328
    OpenUrlAbstract
  15. 15.↵
    1. Heilman C. A.,
    2. Baltimore D.
    HIV vaccines—where are we going? Nat. Med. 4 1998 532 534
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Hirsch V.,
    2. Adger-Johnson D.,
    3. Campbell B.,
    4. Goldstein S.,
    5. Brown C.,
    6. Elkins W. R.,
    7. Montefiori D. C.
    A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.J. Virol. 71 1997 1608 1620
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    Hirsch, V. M., T. R. Fuerst, G. Sutter, M. W. Carroll, L. C. Yang, S. Goldstein, M. Piatak, Jr., W. R. Elkins, W. G. Alvord, D. C. Montefiori, B. Moss, and J. D. Lifson. 1996. Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara. J. Virol.70:3741–3752.
  18. 18.↵
    1. Hirsch V. M.,
    2. Olmsted R. A.,
    3. Murphey-Corb M.,
    4. Purcell R. H.,
    5. Johnson P. R.
    An African non-human primate lentivirus (SIVsm) closely related to HIV-2.Nature 339 1989 389 392
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Hirsch V. M.,
    2. Zack P. M.,
    3. Vogel A. P.,
    4. Johnson P. R.
    Simian immunodeficiency virus infection of macaques: pathogenesis of end-stage disease in characterized by high levels of proviral DNA in tissues.J. Infect. Dis. 163 1991 976 988
    OpenUrlCrossRefPubMedWeb of Science
  20. 20.↵
    1. Hu S.-L.
    Recombinant subunit vaccines against primate lentiviruses.AIDS Res. Hum. Retrovir. 12 1996 451 453
    OpenUrlPubMedWeb of Science
  21. 21.↵
    1. Hu S.-L.,
    2. Abrams K.,
    3. Barber G. N.,
    4. Moran P.,
    5. Zarling J. M.,
    6. Langlois A. J.,
    7. Kuller L.,
    8. Morton W. R.,
    9. Benveniste R. E.
    Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160.Science 255 1992 456 459
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Hu S.-L.,
    2. Fultz P. N.,
    3. McClure H. M.,
    4. Eichberg J. W.,
    5. Thomas E. K.,
    6. Zarling J.,
    7. Singhal M. C.,
    8. Kosowski S. G.,
    9. Swenson R. B.,
    10. Anderson D. C.,
    11. Todaro G.
    Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees.Nature 328 1987 721 723
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Johnson P. R.,
    2. Montefiori D. C.,
    3. Goldstein S.,
    4. Hamm T. E.,
    5. Zhou J.,
    6. Kitov S.,
    7. Haigwood N. L.,
    8. Misher L.,
    9. London W. T.,
    10. Gerin J. L.,
    11. Allison A.,
    12. Purcell R. H.,
    13. Chanock R. M.,
    14. Hirsch V. M.
    Inactivated whole SIV vaccine in macaques: evaluation of protective efficacy against challenge with cell-free virus or infected cells.AIDS Res. Hum. Retrovir. 8 1992 1501 1505
    OpenUrlPubMedWeb of Science
  24. 24.↵
    1. Koup R. A.,
    2. Safrit J. T.,
    3. Cao Y.,
    4. Andrews C. A.,
    5. McLeod G.,
    6. Borkowsky W.,
    7. Farthing C.,
    8. Ho D. D.
    Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.J. Virol. 68 1994 4650 4655
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Langlois A. J.,
    2. Desrosiers R. C.,
    3. Lewis M. G.,
    4. Kewalramani V. N.,
    5. Littman D. R.,
    6. Zhou J. Y.,
    7. Manson K.,
    8. Bolognesi D. P.,
    9. Wyand M. S.,
    10. Montefiori D. C.
    Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus.J. Virol. 72 1998 6950 6955
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Lefrancois L.
    Protection against lethal viral infection by neutralizing and nonneutralizing monoclonal antibodies: distinct mechanisms of action in vivo.J. Virol. 51 1984 208 214
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Letvin N. L.
    Progress in the development of an HIV-1 vaccine.Science 280 1998 1875 1880
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Mascola J. R.,
    2. Lewis M. G.,
    3. Stiegler G.,
    4. Harris D.,
    5. VanCott T. C.,
    6. Hayes D.,
    7. Louder M. K.,
    8. Brown C. R.,
    9. Sapan C. V.,
    10. Frankel S. S.,
    11. Lu Y.,
    12. Robb M. L.,
    13. Katinger H.,
    14. Birx D. L.
    Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies.J. Virol. 73 1999 4009 4018
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Mathews J. H.,
    2. Roehrig J. T.,
    3. Trent D. W.
    Role of complement and the Fc portion of immunoglobulin G in immunity to Venezuelan equine encephalomyelitis virus infection with glycoprotein-specific monoclonal antibodies.J. Virol. 55 1985 594 600
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Means R. E.,
    2. Greenough T.,
    3. Desrosiers R. C.
    Neutralization sensitivity of cell culture-passaged simian immunodeficiency virus.J. Virol. 71 1997 7895 7902
    OpenUrlAbstract/FREE Full Text
  31. 31.↵
    1. Montefiori D. C.
    Role of complement and Fc receptors in the pathogenesis of HIV-1 infection.Springer Semin. Immunopathol. 18 1997 371 390
    OpenUrlCrossRefPubMedWeb of Science
  32. 32.↵
    1. Montefiori D. C.,
    2. Baba T. W.,
    3. Li A.,
    4. Bilska M.,
    5. Ruprecht R. M.
    Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239Δ3 in adult and infant rhesus monkeys.J. Immunol. 157 1996 5528 5535
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    Montefiori, D. C., and T. G. Evans.Toward an HIV-1 vaccine that generates potent, broadly cross-reactive neutralizing antibodies. AIDS Res. Hum. Retrovir., in press.
  34. 34.↵
    1. Moog C. H.,
    2. Fleury J. A.,
    3. Pellegrin I.,
    4. Kirn A.,
    5. Aubertin A. M.
    Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals.J. Virol. 71 1997 3734 3741
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Moore J. P.,
    2. Binley J.
    Envelope's letters boxed into shape.Nature 393 1998 630 631
    OpenUrlCrossRefPubMedWeb of Science
  36. 36.↵
    1. Mozdzanowska K.,
    2. Furchner M.,
    3. Washko G.,
    4. Mozdzanowski J.,
    5. Gerhard W.
    A pulmonary influenza virus infection in SCID mice can be cured by treatment with hemagglutinin-specific antibodies that display very low virus-neutralizing activity in vitro.J. Virol. 71 1997 4347 4355
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Nakanaga K.,
    2. Yamanouchi K.,
    3. Fujiwara K.
    Protective effect of monoclonal antibodies on lethal mouse hepatitis virus infection in mice.J. Virol. 59 1986 168 171
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Nara P. L.,
    2. Garrity R.
    Deceptive imprinting: a cosmopolitan strategy for complicating vaccination.Vaccine 16 1998 1780 1787
    OpenUrlCrossRefPubMedWeb of Science
  39. 39.↵
    1. Ourmanov I.,
    2. Brown C. R.,
    3. Moss B.,
    4. Carroll M.,
    5. Wyatt L.,
    6. Pletneva L.,
    7. Goldstein S.,
    8. Venzon D.,
    9. Hirsch V. M.
    Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in Macaques challenged with pathogenic SIV.J. Virol. 74 2000 2740 2751
    OpenUrlAbstract/FREE Full Text
  40. 40.↵
    1. Pellegrin I.,
    2. Legrand E.,
    3. Neau D.,
    4. Bonot P.,
    5. Masquelier B.,
    6. Pellegrin J.-L.,
    7. Ragnaud J.-M.,
    8. Bernard N.,
    9. Fleury H. J. A.
    Kinetics of appearance of neutralizing antibodies in 12 patients with primary or recent HIV-1 infection and relationship with plasma and cellular viral loads.J. Acquir. Immune Defic. Syndr. 11 1996 438 447
    OpenUrl
  41. 41.↵
    1. Pialoux G.,
    2. Excler J.-L.,
    3. Rivière Y.,
    4. Gonzalez-Canali G.,
    5. Feuillie V.,
    6. Couland P.,
    7. Gluckman J.-C.,
    8. Matthews T. J.,
    9. Meignier B.,
    10. Kieny M.-P.,
    11. Gonnet P.,
    12. Diaz I.,
    13. Méric C.,
    14. Paoletti E.,
    15. Tartaglia J.,
    16. Salomon H.,
    17. Plotkin S.
    A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI).AIDS Res. Hum. Retrovir. 11 1995 373 381
    OpenUrlCrossRefPubMedWeb of Science
  42. 42.↵
    1. Pilgrim A. K.,
    2. Pantaleo G.,
    3. Cohen O. J.,
    4. Fink L. M.,
    5. Zhou J. Y.,
    6. Zhou J. T.,
    7. Bolognesi D. P.,
    8. Fauci A. S.,
    9. Montefiori D. C.
    Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term nonprogressive infection.J. Infect. Dis. 176 1997 924 932
    OpenUrlCrossRefPubMedWeb of Science
  43. 43.↵
    1. Pincus S. H.,
    2. Cole R.,
    3. Ireland R.,
    4. McAtee F.,
    5. Fujisawa R.,
    6. Portis J.
    Protective efficacy of nonneutralizing monoclonal antibodies in acute infection with murine leukemia virus.J. Virol. 69 1995 7152 7158
    OpenUrlAbstract/FREE Full Text
  44. 44.↵
    1. Schmaljohn A. L.,
    2. Johnson E. D.,
    3. Dalrymple J. M.,
    4. Cole G. A.
    Nonneutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis.Nature (London) 297 1982 70 72
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Seth A.,
    2. Ourmanov I.,
    3. Kuroda M. J.,
    4. Schimtz J. E.,
    5. Carroll M. W.,
    6. Wyatt L. S.,
    7. Moss B.,
    8. Forman M. A.,
    9. Hirsch V. M.,
    10. Letvin N. L.
    Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer.Proc. Natl. Acad. Sci. USA 95 1998 10112 10116
    OpenUrlAbstract/FREE Full Text
  46. 46.↵
    1. Shibata R.,
    2. Igarashi T.,
    3. Haigwood N.,
    4. Buckler-White A.,
    5. Ogert R.,
    6. Ross W.,
    7. Willey R.,
    8. Cho M. W.,
    9. Martin M. A.
    Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys.Nat. Med. 5 1999 204 210
    OpenUrlCrossRefPubMedWeb of Science
  47. 47.↵
    1. Tyler D. S.,
    2. Lyerly H. K.,
    3. Weinhold K. J.
    Anti-HIV-1 ADCC: a minireview.AIDS Res. Hum. Retrovir. 5 1989 557 563
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Van Rompay K. K. A.,
    2. Berardi C. J.,
    3. Dillard-Telm S.,
    4. Tarara R. P.,
    5. Canfield D. R.,
    6. Valverde C. R.,
    7. Montefiori D. C.,
    8. Stefano-Cole K.,
    9. Montelaro R. C.,
    10. Miller C. J.,
    11. Marthas M. L.
    Passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection.J. Infect. Dis. 177 1998 1247 1259
    OpenUrlCrossRefPubMedWeb of Science
  49. 49.↵
    1. Wyatt R.,
    2. Sodroski J.
    The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens.Science 280 1998 1884 1888
    OpenUrlAbstract/FREE Full Text
  50. 50.↵
    1. Zhang J.-Y.,
    2. Martin L. N.,
    3. Watson E. A.,
    4. Montelaro R. C.,
    5. West M.,
    6. Epstein L.,
    7. Murphey-Corb M.
    Simian immunodeficiency virus/Delta-induced immunodeficiency disease in rhesus monkeys: relation of antibody response and antigenemia.J. Infect. Dis. 158 1988 1277 1286
    OpenUrlCrossRefPubMedWeb of Science
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques
Ilnour Ourmanov, Miroslawa Bilska, Vanessa M. Hirsch, David C. Montefiori
Journal of Virology Mar 2000, 74 (6) 2960-2965; DOI: 10.1128/JVI.74.6.2960-2965.2000

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Virology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques
(Your Name) has forwarded a page to you from Journal of Virology
(Your Name) thought you would be interested in this article in Journal of Virology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques
Ilnour Ourmanov, Miroslawa Bilska, Vanessa M. Hirsch, David C. Montefiori
Journal of Virology Mar 2000, 74 (6) 2960-2965; DOI: 10.1128/JVI.74.6.2960-2965.2000
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Antibodies, Viral
HIV Envelope Protein gp120
Membrane Glycoproteins
Simian Acquired Immunodeficiency Syndrome
Vaccines, DNA
Viral Envelope Proteins
Viral Vaccines

Related Articles

Cited By...

About

  • About JVI
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #Jvirology

@ASMicrobiology

       

 

JVI in collaboration with

American Society for Virology

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0022-538X; Online ISSN: 1098-5514