Citrate-mediated disaggregation of rotavirus particles in RotaTeq vaccine.


:For the routine manufacture of live virus vaccines, virus is diluted into a formulation buffer to stabilize it for long-term storage, and to facilitate vaccine administration. The characteristics of this buffer are dependent on the storage temperature of the vaccine, as well as the desired characteristics of the product. The formulation buffer for RotaTeq, Merck's live, pentavalent, oral rotavirus vaccine to prevent rotavirus gastroenteritis was developed as a fully liquid solution that requires no pre-feeding prior to administration, and is stable for 24 months at refrigerated temperatures. In studying the effects of the formulation buffer on the live virus contained within RotaTeq, we observed that the formulation buffer also directly impacts the state of rotavirus aggregation. This observation, termed "the matrix effect," was first noted as an approximately 50% increase in measured in vitro infectivity, following dilution of the virus into the buffer. Subsequent experiments confirmed that citrate in the formulation buffer facilitates the disaggregation of viral particles, likely through a carboxylic-acid mediated interaction. For vaccine manufacture, bulk virus is titered and subsequently diluted to a target concentration for dosing. Aggregation of the virus and subsequent inaccurate measurement of the amount of virus contained in either the bulk sample or in the final dosing container could lead to an inability to accurately predict final vaccine concentrations. Thus, discerning the nature and extent of the matrix effect was key principally for providing an accurate prediction of final virus concentration upon dilution, to ensure a robust manufacturing process. In addition, understanding potential contributions of the formulation buffer to clinical efficacy of the vaccine was critical. Clinical data have confirmed that the citrate-mediated disaggregation had no measurable impact on vaccine safety, immunogenicity, or efficacy.


Antiviral Res


Antiviral research


Peterson SE,Wang S,Ranheim T,Owen KE




Has Abstract


2006-02-01 00:00:00














  • Retinoic acid receptor β, a potential therapeutic target in the inhibition of adenovirus replication.

    abstract::Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficia...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Wang X,Zhang Q,Zhou Z,Liu M,Chen Y,Li J,Xu L,Guo J,Li Q,Yang J,Wang S

    更新日期:2018-04-01 00:00:00

  • FoxO4 inhibits HBV core promoter activity through ERK-mediated downregulation of HNF4α.

    abstract::Hepatitis B virus (HBV) infection remains a global health problem, causing nearly one million deaths annually. Forkhead box O (FoxO) transcription factors play important roles in modulating diverse physiological processes. Recent studies show that FoxOs are involved in antiviral responses. In present investigation, we...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Li L,Li Y,Xiong Z,Shu W,Yang Y,Guo Z,Gao B

    更新日期:2019-10-01 00:00:00

  • Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation.

    abstract::Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurr...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Huang L,Yang M,Yuan Y,Li X,Kuang E

    更新日期:2017-02-01 00:00:00

  • Immunogenicity and protective efficacy of recombinant major envelope protein (rH3L) of buffalopox virus in animal models.

    abstract::Buffalopox virus, a zoonotic Indian vaccinia-like virus, is responsible for contagious disease affecting mainly buffaloes, cattle and humans. H3L gene, encoding for an immunodominant major envelope protein of intracellular mature virion of orthopoxviruses, is highly conserved and found to elicit neutralizing antibodie...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Kumar A,Yogisharadhya R,Venkatesan G,Bhanuprakash V,Shivachandra SB

    更新日期:2016-02-01 00:00:00

  • Synergistic inhibition of HIV-1 infection by combinations of soluble polyanions with other potential microbicides.

    abstract::Several polyanionic compounds with potential for use as topically applied microbicides to prevent HIV-1 sexual transmission, such as PRO 2000, are currently in phase III clinical efficacy trials. Microbicidal formulations may well comprise combinations of inhibitors to increase potency, reduce dose and minimize proble...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Gantlett KE,Weber JN,Sattentau QJ

    更新日期:2007-09-01 00:00:00

  • Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation.

    abstract::The influenza A virus (IAV) NS1 protein is one of the major regulators of pathogenicity, being able to suppress innate immune response and host protein synthesis. In this study we identified the human micro RNA hsa-miR-1307-3p as a novel potent suppressor of NS1 expression and influenza virus replication. Transcriptom...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Bavagnoli L,Campanini G,Forte M,Ceccotti G,Percivalle E,Bione S,Lisa A,Baldanti F,Maga G

    更新日期:2019-11-01 00:00:00

  • Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere.

    abstract::Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsib...

    journal_title:Antiviral research

    pub_type: 历史文章,杂志文章,评审


    authors: Velasco-Villa A,Escobar LE,Sanchez A,Shi M,Streicker DG,Gallardo-Romero NF,Vargas-Pino F,Gutierrez-Cedillo V,Damon I,Emerson G

    更新日期:2017-07-01 00:00:00

  • The efficacy of combined therapy of arsenic trioxide and alpha interferon in human T-cell leukemia virus type-1-infected squirrel monkeys (Saimiri sciureus).

    abstract::Human T-cell lymphotropic virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis owing to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha interferon (IFN-alpha) give rise to some response and improve the prognosis of ATLL, alternative therapies are nee...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Heraud JM,Mortreux F,Merien F,Contamin H,Mahieux R,Pouliquen JF,Wattel E,Gessain A,de Thé H,Bazarbachi A,Hermine O,Kazanji M

    更新日期:2006-07-01 00:00:00

  • Lifecycle modelling systems support inosine monophosphate dehydrogenase (IMPDH) as a pro-viral factor and antiviral target for New World arenaviruses.

    abstract::Infection with Junín virus (JUNV) is currently being effectively managed in the endemic region using a combination of targeted vaccination and plasma therapy. However, the long-term sustainability of plasma therapy is unclear and similar resources are not available for other New World arenaviruses. As a result, there ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Dunham EC,Leske A,Shifflett K,Watt A,Feldmann H,Hoenen T,Groseth A

    更新日期:2018-09-01 00:00:00

  • Baicalin inhibits autophagy induced by influenza A virus H3N2.

    abstract::Baicalin, a natural product isolated from Scutellariaradix, has been reported to have significant in vivo and in vitro anti-influenza virus activity, but the underlying mechanism remains poorly understood. In this study, we found that baicalin inhibited autophagy induced by influenza virus A3/Beijing/30/95 (H3N2) in b...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Zhu HY,Han L,Shi XL,Wang BL,Huang H,Wang X,Chen DF,Ju DW,Feng MQ

    更新日期:2015-01-01 00:00:00

  • Activities of JNJ63623872 and oseltamivir against influenza A H1N1pdm and H3N2 virus infections in mice.

    abstract::JNJ63623872 (formerly known as VX-787) is an inhibitor of influenza A virus polymerases through interaction with the viral PB2 subunit. This interaction blocks the cap-snatching activity of the virus that is essential for virus replication. Previously published work has documented antiviral activity of JNJ63623872 in ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Smee DF,Barnard DL,Jones SM

    更新日期:2016-12-01 00:00:00

  • In vitro and in vivo anti-hepatitis B virus activities of a plant extract from Geranium carolinianum L.

    abstract::Natural products provide a large reservoir of potentially active agents with anti-hepatitis B virus (HBV) activity. We examined the effect of the polyphenolic extract from Geranium carolinianum L. (PPGC) on HBV replication both in vitro and in vivo. In the human HBV-transfected liver cell line HepG(2) 2.2.15, PPGC eff...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Li J,Huang H,Feng M,Zhou W,Shi X,Zhou P

    更新日期:2008-08-01 00:00:00

  • Antiviral effect of cyclopentenone prostaglandins on vesicular stomatitis virus replication.

    abstract::Prostaglandins are potentially useful antiviral agents, however their mechanism of action is unclear. Recent evidence suggests that RNA transcription of vesicular stomatitis virus (VSV) is inhibited by prostaglandins (Bader and Ankel, J. Gen. Virol. 71, 2823-2832, 1990). Prostaglandins are known to have multiple effec...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Parker J,Ahrens PB,Ankel H

    更新日期:1995-01-01 00:00:00

  • Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

    abstract::Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Ikram A,Obaid A,Awan FM,Hanif R,Naz A,Paracha RZ,Ali A,Janjua HA

    更新日期:2017-01-01 00:00:00

  • Antiviral activity of natural and synthetic β-carbolines against dengue virus.

    abstract::Dengue virus (DENV) is the most prevalent mosquito borne viral pathogen worldwide. In this work we first evaluated the antiviral activity of natural and synthetic β-carbolines against DENV-2 multiplication in cell cultures. We determined that the natural β-carboline harmol and a synthetic harmine derivative, 9N-methyl...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Quintana VM,Piccini LE,Panozzo Zénere JD,Damonte EB,Ponce MA,Castilla V

    更新日期:2016-10-01 00:00:00

  • Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate.

    abstract::The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZTp(4)A. In the present study, we report that AZTp(4)A is an excellent subs...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Pitcher WH 3rd,Kirby TW,DeRose EF,London RE

    更新日期:2003-05-01 00:00:00

  • Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro.

    abstract:BACKGROUND:By modulating the antiviral immune response via vitamin D receptor, the active form of vitamin D (1,25-dihydroxyvitamin D, calcitriol) could play a central role in protection against respiratory virus infections. This in vitro study tested the hypothesis that respiratory viruses modulate vitamin D receptor e...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Telcian AG,Zdrenghea MT,Edwards MR,Laza-Stanca V,Mallia P,Johnston SL,Stanciu LA

    更新日期:2017-01-01 00:00:00

  • Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections.

    abstract::As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 kerati...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Maudgal PC,De Clercq E,Missotten L

    更新日期:1984-10-01 00:00:00

  • Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.

    abstract::One of the plant extracts, glycyrrhizin (GL) was investigated for its antiviral action on varicella-zoster virus (VZV) in vitro. When human embryonic fibroblast (HEF) cells were treated with GL after inoculation of virus (post-treatment), the average 50%-inhibitory dose (ID50) for five VZV strains was 0.71 mM, and the...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Baba M,Shigeta S

    更新日期:1987-02-01 00:00:00

  • Antiretroviral activities of hypericin and rose bengal: photodynamic effects on Friend leukemia virus infection of mice.

    abstract::The ability of hypericin to protect mice from splenomegaly resulting from infection with Friend leukemia virus (FLV) was re-examined in light of recent evidence showing that light is absolutely required for this drug's antiviral activity. FLV-induced splenomegaly was not prevented or ameliorated in mice injected with ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Stevenson NR,Lenard J

    更新日期:1993-06-01 00:00:00

  • Lactoferrin inhibits human papillomavirus binding and uptake in vitro.

    abstract::Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein secreted in milk, saliva, tears, seminal fluid, endocervix and vaginal secretions. LF is an important player in the defence against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesv...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Drobni P,Näslund J,Evander M

    更新日期:2004-10-01 00:00:00

  • Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.

    abstract::Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Smee DF,Evans WJ,Nicolaou KC,Tarbet EB,Day CW

    更新日期:2016-07-01 00:00:00

  • Clinical management and infection control of SARS: lessons learned.

    abstract::The outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience o...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审


    authors: Cheng VC,Chan JF,To KK,Yuen KY

    更新日期:2013-11-01 00:00:00

  • Intracellular delivery of nucleoside monophosphates through a reductase-mediated activation process.

    abstract::On the basis of three different models (namely: ddU, AZT and PMEA), mononucleotide phosphotriester derivatives were designed to be able to liberate the corresponding monophosphate (or phosphonate) inside the cell through a reductase-mediated activation process. It was demonstrated that the use of bis[S-(2-hydroxyethyl...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Puech F,Gosselin G,Lefebvre I,Pompon A,Aubertin AM,Kirn A,Imbach JL

    更新日期:1993-10-01 00:00:00

  • Protection of a novel epitope-RNA VLP double-effective VLP vaccine for foot-and-mouth disease.

    abstract::Foot and mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. Previously, we found that the epitope peptide EP141-160 displayed on virus-like particles (VLP) for use as a vaccine showed high immunoreactivity and conferred partially effective protection to animals. In this study, we first ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Dong YM,Cai JC,Chen HT,Chen L

    更新日期:2016-10-01 00:00:00

  • In silico study supports the efficacy of a reduced dose regimen for stavudine.

    abstract::Stavudine (d4T) is used extensively as part of HAART in resource poor settings, despite its toxicities. The revised WHO guidelines specify replacement of d4T with less toxic but more expensive drugs when feasible, and that d4T doses be standardized to 30 mg twice daily (bid) (irrespective of body-weight), from the app...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Hurwitz SJ,Schinazi RF

    更新日期:2011-11-01 00:00:00

  • Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.

    abstract::A newly synthesized imide derivative of 3-nitro-1,8-naphthalic acid, 5-amino-2-(2-dimethylaminoethyl)benzo-[de]-isoquinolin-1,3-dione (designated M-FA-142), was tested on chick embryo cells against herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), and on Vero cells against African swine fever virus (ASFV). ...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: García Gancedo A,Gil-Fernández C,Vilas P,Pérez S,Rodriguez F,Paez E,Braña MF,Roldán CM

    更新日期:1984-08-01 00:00:00

  • Antiviral drug susceptibility assays: going with the flow.

    abstract::This review describes the procedures for the use of fluorochrome labeled monoclonal antibodies and flow cytometry for the detection and quantification of virus infected cells. The application of this technology for (1) identifying virus infected cells in clinical specimens obtained from human cytomegalovirus (HCMV) an...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审


    authors: McSharry JJ

    更新日期:1999-08-01 00:00:00

  • Natural killer cell activity and function in chronic HCV-infected patients during peg interferon and ribavirin: early effects of active substance use.

    abstract::In Western countries, chronic hepatitis C virus (HCV)-infection mostly affects former and active substance users. The effect of active substance use on interferon (IFN)-responsiveness and therapy efficacy is not well understood. In this study, we compared natural killer (NK) cell activity and function in healthy contr...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Hotho DM,Kreefft K,Groothuismink ZM,Janssen HL,de Knegt RJ,Boonstra A

    更新日期:2013-03-01 00:00:00

  • Alterations in favipiravir (T-705) pharmacokinetics and biodistribution in a hamster model of viral hemorrhagic fever.

    abstract::Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, in...

    journal_title:Antiviral research

    pub_type: 杂志文章


    authors: Gowen BB,Sefing EJ,Westover JB,Smee DF,Hagloch J,Furuta Y,Hall JO

    更新日期:2015-09-01 00:00:00