An experimental chemically inactivated HIV-1 vaccine induces antibodies that neutralize homologous and heterologous viruses

Race, Esther; Frezza, Pino; Stephens, D. M.; Davis, David A.; Polyanskaya, Natasha; Cranage, Martin; Oxford, John

doi:10.1016/0264-410x(95)80011-2

Cited by 17 publications

(7 citation statements)

References 28 publications

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“…BEI is used for the inactivation of many viruses, such as FMDV [70], RRV [75], sheep pox [76], HIV [77], Nipah virus [78], HNV [67] and PRRSV (Table 6) [79].…”

Section: Aminoethyl Ethylene Iminementioning

confidence: 99%

“…Vaccinated lambs were protected on challenge up to 6-months postvaccination [76]. Race et al have shown that the experimental BEI-inactivated HIV vaccine induces virus-neutralizing antibodies against both the homologous vaccine strain and a heterologous virus strain [77]. Also, virus-specific antibodies could be induced against BEI-inactivated Nipah virus; however, these did not neutralizing the virus in vitro [78].…”

Section: Aminoethyl Ethylene Iminementioning

confidence: 99%

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Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

Delrue

Verzele

Madder

et al. 2012

Expert Review of Vaccines

166

150

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The aim of this review is to make researchers aware of the benefits of an efficient quality control system for prediction of a developed vaccine's efficacy. Two major goals should be addressed when inactivating a virus for vaccine purposes: first, the infectious virus should be inactivated completely in order to be safe, and second, the viral epitopes important for the induction of protective immunity should be conserved after inactivation in order to have an antigen of high quality. Therefore, some problems associated with the virus inactivation process, such as virus aggregate formation, protein crosslinking, protein denaturation and degradation should be addressed before testing an inactivated vaccine in vivo

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“…BEI is used for the inactivation of many viruses, such as FMDV [70], RRV [75], sheep pox [76], HIV [77], Nipah virus [78], HNV [67] and PRRSV (Table 6) [79].…”

Section: Aminoethyl Ethylene Iminementioning

confidence: 99%

Section: Aminoethyl Ethylene Iminementioning

confidence: 99%

Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

Delrue

Verzele

Madder

et al. 2012

Expert Review of Vaccines

166

150

View full text Add to dashboard Cite

show abstract

“…Env can be presented on membranes in several ways, including liposomes, inactivated viruses and virus-like particles (VLPs) or pseudovirions (Grovit-Ferbas et al, 2000;Grundner et al, 2002;Race et al, 1995;Rossio et al, 1998). Particulate vaccines have a long history of success for a variety of diseases, including those caused by rotavirus (Conner et al, 1996), norwalk virus (Harrington et al, 2002), tick-borne encephalitis virus (Aberle et al, 1999) and HCV (Issel et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120

et al. 2007

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To assess the potential of native Envelope glycoprotein (Env) trimers as neutralizing antibody vaccines, we immunized guinea pigs with three types of VLPs and soluble gp120. Particles included "SOS-VLPs" (bearing disulfide-shackled functional trimers), "UNC-VLPs" (bearing uncleaved nonfunctional Env) and "naked VLPs" (bearing no Env). The SOS-VLPs were found to have a density of about 27 native trimers per particle, approximately twice that of live inactivated HIV-1 preparations. As immunogens, UNC- and SOS-VLP rapidly elicited anti-gp120 antibodies focused on the V3 loop and the gp120 coreceptor binding site. Reactivity to the gp41 immunodominant domain was absent in SOS-VLP sera, presumably because gp120-gp41 association is stabilized, effectively covering this epitope. Gp120-immune sera reacted with the receptor binding sites of gp120 and were less focused on the V3 loop. Some Env-VLP sera neutralized primary isolates at modest titers. The measurement of neutralization was found to be affected by the cell lines used. Depending on the assay particulars, non-Env specific antibodies in VLP sera could enhance infection, or nonspecifically neutralize. However, a neutralization assay using TZM-BL cells was essentially clear of these effects. We also describe a native trimer binding assay to confirm neutralization activity in a manner that completely eliminates nonspecific effects. Overall, our data suggests that Env-VLP sera were primarily focused on nonfunctional forms of Env on VLP surfaces, possibly gp120/gp41 monomers and not the trimers. Therefore, to make progress toward a more effective VLP-based vaccine, we will need to find ways to refocus the attention of B cells on native trimers.

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“…At least five biotech companies, Acrogen, Behringwerke AG, Retroscreen, HIV-VAC, and Aphios, have attempted this approach in the past [117][118][119][120]. Unfortunately, all these companies had largely given up due to lack of interest and funding.…”

Section: Hiv Virion-based Vaccines Other Than Remunementioning

confidence: 99%

Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

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Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

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An experimental chemically inactivated HIV-1 vaccine induces antibodies that neutralize homologous and heterologous viruses

Cited by 17 publications

References 28 publications

Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120

Therapeutic AIDS Vaccines

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