Citrate-mediated disaggregation of rotavirus particles in RotaTeq vaccine.

Abstract:

: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.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Peterson SE,Wang S,Ranheim T,Owen KE

doi

10.1016/j.antiviral.2005.11.001

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

107-15

issue

2

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(05)00235-4

journal_volume

69

pub_type

杂志文章
  • Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L.

    abstract::RNase L is a cellular endoribonuclease that is activated by 2',5'-linked oligoadenylates (2-5A), which are unique and specific ligands synthesized by a family of interferon-inducible, dsRNA-activated enzymes named oligoadenylate synthetases. In the typical antiviral pathway, activated RNase L degrades viral and cellul...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2014.01.021

    authors: Park IH,Kwon YC,Ryu WS,Ahn BY

    更新日期:2014-04-01 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

    doi:10.1016/j.antiviral.2012.12.025

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

    更新日期:2013-03-01 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

    doi:10.1016/j.antiviral.2008.03.001

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

    更新日期:2008-08-01 00:00:00

  • Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections.

    abstract::The latent reservoir of HIV-1 in resting memory CD4+ T cells serves as a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 is proposed as a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current latency reversal agents (LRAs), identification of new LRAs ...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2019.104555

    authors: Yang H,Li X,Yang X,Lu P,Wang Y,Jiang Z,Pan H,Zhao L,Zhu Y,Khan IU,Shen Y,Lu H,Zhang T,Jiang G,Ma Z,Wu H,Zhu H

    更新日期:2019-09-01 00:00:00

  • Potential economic benefits of eliminating canine rabies.

    abstract::Although canine rabies has been eliminated from industrialized countries, infected dogs remain the primary source of human and livestock exposures in Asia, Africa and much of South America. Human deaths are the most important direct economic impact of canine rabies, followed by livestock losses and the cost of PEP, wh...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:10.1016/j.antiviral.2013.03.004

    authors: Shwiff S,Hampson K,Anderson A

    更新日期:2013-05-01 00:00:00

  • Immunological and biochemical characterizations of coxsackievirus A6 and A10 viral particles.

    abstract::Childhood exanthema caused by different serotypes of coxsackievirus (CV-A) and enterovirus A71 (EV-A71) has become a serious global health problem; it is commonly known as hand, foot, and mouth disease (HFMD). Current EV-A71 vaccine clinical trials have demonstrated that human antibody responses generated by EV-A71 va...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2016.02.008

    authors: Liu CC,Guo MS,Wu SR,Lin HY,Yang YT,Liu WC,Chow YH,Shieh DB,Wang JR,Chong P

    更新日期:2016-05-01 00:00:00

  • Effect of antiviral treatment in older patients hospitalized with confirmed influenza.

    abstract::Seasonal influenza causes significant morbidity and mortality in people aged ≥65 years. Antiviral treatment can reduce complications and disease severity. The objective of this study was to investigate the effect of antiviral treatment in patients aged ≥65 years hospitalized with confirmed influenza in preventing inte...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2020.104785

    authors: Soldevila N,Toledo D,Ortiz de Lejarazu R,Tamames S,Castilla J,Astray J,Fernández MA,Martín V,Egurrola M,Morales Suárez-Varela M,Domínguez À,Working Group of Project PI12\/02079.

    更新日期:2020-06-01 00:00:00

  • Inhibition of human parainfluenza virus type 3 infection by novel small molecules.

    abstract::Human parainfluenza virus type 3 (HPIV3) is an important respiratory tract pathogen of infants and children. There are no vaccines or antivirals currently approved for prevention or treatment of HPIV3 infection. Towards developing an antiviral therapy to combat HPIV3 infection, we have established a green fluorescent ...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2007.09.001

    authors: Mao H,Thakur CS,Chattopadhyay S,Silverman RH,Gudkov A,Banerjee AK

    更新日期:2008-02-01 00:00:00

  • Inhibitory effect of Ephedrae herba, an oriental traditional medicine, on the growth of influenza A/PR/8 virus in MDCK cells.

    abstract::Using several herbal extracts, we investigated whether certain Kampo medicines exert an inhibitory effect on the acidification of intracellular compartments such as endosomes and lysosomes (referred to as ELS), and thereby inhibit the growth of influenza A virus in Madin-Darby canine kidney cells. The vital fluorescen...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/s0166-3542(99)00067-4

    authors: Mantani N,Andoh T,Kawamata H,Terasawa K,Ochiai H

    更新日期:1999-12-31 00:00:00

  • Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide.

    abstract::Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136-154)] linked through thioether bonds to a T-cell epitope [3A(21-35)] of FMDV [B4T(thi)] e...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2016.03.005

    authors: Blanco E,Guerra B,de la Torre BG,Defaus S,Dekker A,Andreu D,Sobrino F

    更新日期:2016-05-01 00:00:00

  • Algorithms for the interpretation of HIV-1 genotypic drug resistance information.

    abstract::Drug resistance testing has proven its use to guide treatment decisions in HIV-1 infected patients. Genotyping is the preferred technique for clinical drug resistance testing. Many factors complicate the interpretation of mutations towards therapy response, such that an interpretation system is necessary to help the c...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:10.1016/j.antiviral.2006.05.003

    authors: Vercauteren J,Vandamme AM

    更新日期:2006-09-01 00:00:00

  • Antiviral properties of extract of Opuntia streptacantha.

    abstract::An extract of the cactus plant Opuntia streptacantha inhibited intracellular virus replication and inactivated extracellular virus. Inhibition of virus replication also occurred following pre-infection treatment--a favourable finding in terms of in-vivo limitation of virus disease. There was inhibition of both DNA and...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/0166-3542(95)00839-x

    authors: Ahmad A,Davies J,Randall S,Skinner GR

    更新日期:1996-05-01 00:00:00

  • Novel L-lyxo and 5'-deoxy-5'-modified TSAO-T analogs: synthesis and anti-HIV-1 activity.

    abstract::Novel L-lyxo-TSAO-T analogs with an inverted configuration at the C-4'-position of the sugar moiety and 5'-deoxy-5'-modified TSAO-T derivatives have been prepared and evaluated for their inhibitory effect on human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) replication in cell culture. None of the compoun...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/s0166-3542(95)00989-2

    authors: Ingate S,De Clercq E,Balzarini J,Camarasa MJ

    更新日期:1996-11-01 00:00:00

  • Enhancement by muramyldipeptides of the activities of early-type inducers of interferon.

    abstract::A synthetic muramyldipeptide (MDP) and two analogues, B30-MDP and MDP-Lys(L18), augmented serum interferon (IFN) production in mice by the inducers lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly I:C), and also augmented immune IFN production induced by purified protein derivative (PPD) in myco...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/0166-3542(85)90004-x

    authors: Ikeda S,Matsuda Y,Nishimura C

    更新日期:1985-12-01 00:00:00

  • A bacterial artificial chromosome (BAC)-vectored noninfectious replicon of SARS-CoV-2.

    abstract::Vaccines and antiviral agents are in urgent need to stop the COVID-19 pandemic. To facilitate antiviral screening against SARS-CoV-2 without requirement for high biosafety level facility, we developed a bacterial artificial chromosome (BAC)-vectored replicon of SARS-CoV-2, nCoV-SH01 strain, in which secreted Gaussia l...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2020.104974

    authors: Zhang Y,Song W,Chen S,Yuan Z,Yi Z

    更新日期:2021-01-01 00:00:00

  • Are in vitro hepatitis B core promoter mutations important for clinical alterations in viral load?

    abstract::In vitro studies of HBV core promoter mutations in hepatoma cell lines suggest that some mutations in core promoter transcription factor binding sites result in reduced core promoter activity and viral replication. We sought to validate this hypothesis using clinical samples with viral load differences before and afte...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2005.11.005

    authors: Cheng Y,Seet BL,Ong CS,Wasser S,Tan TM,Peter FJ,Lim SG

    更新日期:2006-03-01 00:00:00

  • Packaging signals in the 5'-ends of influenza virus PA, PB1, and PB2 genes as potential targets to develop nucleic-acid based antiviral molecules.

    abstract::In a previous study a 15-mer phosphorothioate oligonucleotide (S-ON) derived from the packaging signal in the 5' end of segment 1 (PB2) of influenza A virus (designated 5-15b) proved markedly inhibitory to virus replication. Here we investigated whether analogous inhibitory S-ONs targeting the 5' end of segments 2 (PB...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2011.06.013

    authors: Giannecchini S,Wise HM,Digard P,Clausi V,Del Poggetto E,Vesco L,Puzelli S,Donatelli I,Azzi A

    更新日期:2011-10-01 00:00:00

  • The ectodomain of rabies virus glycoprotein determines dendritic cell activation.

    abstract::The immune evasion of wild-type (wt) rabies virus (RABV) has been attributed to its glycoprotein (G), particularly to their inefficiency to bind/enter into dendritic cells (DCs). However, the domain responsible for G-mediated DC activation is not clear. In the present study, attempts were made to map the domain(s) on ...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2017.01.022

    authors: Huang J,Zhang Y,Huang Y,Gnanadurai CW,Zhou M,Zhao L,Fu ZF

    更新日期:2017-05-01 00:00:00

  • Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1 subtypes and recombinants.

    abstract::Transcriptional activation of HIV-1 gene expression is partially controlled by the interaction between viral and cellular transcription factors acting at HIV-1 long terminal repeat (LTR) sequences. HIV-1 subtyping at LTR region and nucleotide LTR variability from clinical samples in 48 subjects carrying different HIV-...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2010.08.007

    authors: de Arellano ER,Alcamí J,López M,Soriano V,Holguín A

    更新日期:2010-11-01 00:00:00

  • The potential use of influenza virus as an agent for bioterrorism.

    abstract::Influenza A virus has been responsible for widespread human epidemics because it is readily transmitted from humans to humans by aerosol. Recent events have highlighted the potential of influenza A virus as a bioterrorist weapon: the high virulence of the influenza A virus that infected people in Hong Kong in 1997; an...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:10.1016/s0166-3542(02)00207-3

    authors: Krug RM

    更新日期:2003-01-01 00:00:00

  • Inhibition of SARS-CoV replication by siRNA.

    abstract::Serious outbreaks of severe acute respiratory syndrome (SARS), caused by the newly discovered coronavirus SARS-CoV, occurred between late 2002 and early 2003 and there is an urgent need for effective antiviral agents. RNA interference in animals and post-transcriptional gene silencing plants is mediated by small doubl...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2004.09.005

    authors: Wu CJ,Huang HW,Liu CY,Hong CF,Chan YL

    更新日期:2005-01-01 00:00:00

  • Antiviral activity of theaflavin digallate against herpes simplex virus type 1.

    abstract::Tea is the second most consumed drink in the world. The beneficial effects of tea have been mostly attributed to its catechin content. Black tea is derived from the leaves of Camellia sinensis plant, and it is rich in theaflavin polyphenols, in particular theaflavin (TF1), theaflavin-3-monogallate (TF2A), theaflavin-3...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2015.03.009

    authors: de Oliveira A,Prince D,Lo CY,Lee LH,Chu TC

    更新日期:2015-06-01 00:00:00

  • Susceptibility of human influenza viruses from Australasia and South East Asia to the neuraminidase inhibitors zanamivir and oseltamivir.

    abstract::Human influenza viruses isolated from Australasia (Australia and New Zealand) and South East Asia were analysed to determine their sensitivity to the NA inhibitor drugs, zanamivir and oseltamivir. A total of 532 strains isolated between 1998 and 2002 were tested using a fluorescence-based assay to measure the relative...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2003.11.008

    authors: Hurt AC,Barr IG,Hartel G,Hampson AW

    更新日期:2004-04-01 00:00:00

  • A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    abstract::Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In t...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2015.10.019

    authors: Yang JR,Chen CY,Kuo CY,Cheng CY,Lee MS,Cheng MC,Yang YC,Wu CY,Wu HS,Liu MT,Hsiao PW

    更新日期:2016-02-01 00:00:00

  • The L1 protein of human papilloma virus 16 expressed by a fowlpox virus recombinant can assemble into virus-like particles in mammalian cell lines but elicits a non-neutralising humoral response.

    abstract::Human papilloma virus (HPV)-16 is the prevalent genotype associated with cervical tumours. Virus-like-particle (VLP)-based vaccines have proven to be effective in limiting new infections of high-risk HPVs, but their high cost has hampered their use, especially in the poor developing countries. Avipox-based recombinant...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2015.01.012

    authors: Bissa M,Zanotto C,Pacchioni S,Volonté L,Venuti A,Lembo D,De Giuli Morghen C,Radaelli A

    更新日期:2015-04-01 00:00:00

  • Baculovirus expressed herpes simplex virus type 1 glycoprotein C protects mice from lethal HSV-1 infection.

    abstract::A recombinant baculovirus (vAc-gC1) was constructed that expresses the glycoprotein C (gC) gene of herpes simplex virus type 1 (HSV-1). When Sf9 cells were infected with this recombinant, a protein that was smaller in size than authentic HSV-1 gC was detected by Western blotting using anti-gC polyclonal antibody. The ...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/0166-3542(92)90062-a

    authors: Ghiasi H,Kaiwar R,Nesburn AB,Wechsler SL

    更新日期:1992-06-01 00:00:00

  • Hepatitis C virus NS3/4A protease.

    abstract::Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be developed. One of the approaches to anti-HCV drug discovery is the design and development of specific small molecule drugs to inhibit the proteolytic processing of the HC...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:

    authors: Kwong AD,Kim JL,Rao G,Lipovsek D,Raybuck SA

    更新日期:1999-02-01 00:00:00

  • Combined antiviral options for the treatment of chronic hepatitis C.

    abstract::In the absence of antiviral treatment, chronic hepatitis C virus (HCV) infection is a liver disease characterized by the development of necroinflammatory changes and progressive liver fibrosis, leading to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). The approval of ribavirin in combination th...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:10.1016/j.antiviral.2003.08.009

    authors: Medina J,García-Buey L,Moreno-Monteagudo JA,Trapero-Marugán M,Moreno-Otero R

    更新日期:2003-10-01 00:00:00

  • In vitro and in vivo influenza virus-inhibitory effects of viramidine.

    abstract::Viramidine, the 3-carboxamidine derivative of ribavirin, was effective against a spectrum of influenza A (H1N1, H3N2 and H5N1) and B viruses in vitro, with the 50% effective concentration (EC50) ranging from 2 to 32 microg/ml. The mean 50% cytotoxic concentration (CC50) in the MDCK cells used in these experiments was ...

    journal_title:Antiviral research

    pub_type: 杂志文章

    doi:10.1016/j.antiviral.2005.06.003

    authors: Sidwell RW,Bailey KW,Wong MH,Barnard DL,Smee DF

    更新日期:2005-10-01 00:00:00

  • Therapy of chronic hepatitis B virus infection: inhibition of the viral polymerase and other antiviral strategies.

    abstract::Chronic hepatitis B infection remains a major public health problem worldwide. The hepatitis B virus belongs to the family of hepadnaviruses that replicate their DNA genome via a reverse transcription pathway. The chronicity of infection in infected hepatocytes is maintained by the persistence of the viral covalently ...

    journal_title:Antiviral research

    pub_type: 杂志文章,评审

    doi:10.1016/s0166-3542(99)00056-x

    authors: Zoulim F

    更新日期:1999-11-01 00:00:00