Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques

Schulte, Reiner; Suh, You-Suk; Sauermann, Ulrike; Ochieng, Washingtone; Sopper, Sieghart; Kim, Kwang S.; Ahn, So-Shin; Park, Ki S.; Stolte-Leeb, Nicole; Hunsmann, Gerhard; Sung, Young Chul; Stahl–Hennig∥, Christiane

doi:10.1016/j.virol.2008.10.012

Cited by 13 publications

(14 citation statements)

References 59 publications

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“…Only the preimmune serum of macaque 12149 had a background neutralization titer of 1:80. SIV p27CA-and gp130SU-specific IgA antibodies were determined as described previously (17). The IFN-␥ enzymelinked immunosorbent spot (ELISPOT) assay and tetramer staining were performed as reported previously (23).…”

Section: Methodsmentioning

confidence: 99%

Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response

Tenbusch

Ignatius

Temchura

et al. 2012

J Virol

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e To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8 ؉ T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e.g., STEP study). Immune escape mechanisms and the diversity of the circulating HIV strains pose many hurdles for the development of an effective HIV vaccine. In addition, testing the efficacy of HIV vaccines in clinical studies is time-consuming and costly. Therefore, only three vaccine strategies have been tested for efficacy in human volunteers so far. A recombinant protein vaccine based on the gp120 surface protein (AIDSVAX) did not provide protection (5, 13), although antibodies to the vaccine antigen were induced. The lack of efficacy was attributed to the absence of neutralizing antibodies. To explore the efficacy of cellular immune responses, volunteers were also immunized with adenoviral vectors carrying gag, pol, and nef of HIV. However, this did not provide protection either, and in a subgroup of volunteers with preexisting antibodies to the adenoviral vector the susceptibility to acquisition of HIV infection was increased (2). The third vaccine strategy tested for efficacy in human volunteers aimed at the induction of cellular and humoral immune responses by combining an avipox vector carrying gag, protease, and env with the AIDSVAX vaccine. The acquisition of HIV infection was reduced by approximately 30% (15), providing the first evidence that protection from HIV infection by vaccination may be possible.Since such an efficacy is probably too low for general use, we explored the efficacy of a novel complementary prime-boost immunization in nonhuman primates. In our previous study, we compared the immunogenicities of dendritic cell (DC)-ta...

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Section: Methodsmentioning

confidence: 99%

Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response

Tenbusch

Ignatius

Temchura

et al. 2012

J Virol

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“…[63][64][65] Systemic vaccination followed by continued mucosal exposures in the presence of PrEP that is sufficient to prevent established infection may allow more effective development of mucosal response. The possibility of a detrimental interaction between ARV for prevention and vaccination has not yet been assessed.…”

Section: Mucosal Exposure In the Absence Of Chronic Infection Can Indmentioning

confidence: 99%

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Excler

Rida²,

Priddy

et al. 2011

AIDS Research and Human Retroviruses

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While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2Â2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

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“…or by oropharyngeal spray/i.m. [15]. Both strategies elicited SIV-specific IFNg and T-cell proliferative responses in blood, although responses in the oropharyngeal/i.m.…”

Section: Oropharyngeal or Tonsilsmentioning

confidence: 99%

“…Although i.m. immunization can induce mucosal responses, much attention has been focused recently on direct mucosal vaccination to elicit high levels of protection at the site of infection (Table 1) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Nonhuman Primate Researchmentioning

confidence: 99%