Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys

The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

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Protective Efficacy of a Single Immunization of a Chimeric Adenovirus Vector-Based Vaccine against Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

Journal of Virology ◽

10.1128/jvi.00821-09 ◽

2009 ◽

Vol 83 (18) ◽

pp. 9584-9590 ◽

Cited By ~ 28

Author(s):

Dan H. Barouch ◽

Jinyan Liu ◽

Diana M. Lynch ◽

Kara L. O'Brien ◽

Annalena La Porte ◽

...

Keyword(s):

Simian Immunodeficiency Virus ◽

Rhesus Monkeys ◽

Recombinant Adenovirus ◽

Protective Efficacy ◽

Hypervariable Region ◽

Adenovirus Vector ◽

Single Shot ◽

Virus Challenge ◽

Immunodeficiency Virus ◽

Potential Vaccine

ABSTRACT Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.

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Construction, Safety, and Immunogenicity in Nonhuman Primates of a Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine

Journal of Virology ◽

10.1128/jvi.75.16.7290-7304.2001 ◽

2001 ◽

Vol 75 (16) ◽

pp. 7290-7304 ◽

Cited By ~ 153

Author(s):

F. Guirakhoo ◽

J. Arroyo ◽

K. V. Pugachev ◽

C. Miller ◽

Z.-X. Zhang ◽

...

Keyword(s):

Yellow Fever ◽

Rhesus Monkeys ◽

Neutralizing Antibodies ◽

Nonhuman Primates ◽

Protective Efficacy ◽

Vero Cells ◽

Anamnestic Response ◽

Tetravalent Vaccine ◽

Significant Difference ◽

Chimeric Viruses

ABSTRACT We previously reported construction of a chimeric yellow fever-dengue type 2 virus (YF/DEN2) and determined its safety and protective efficacy in rhesus monkeys (F. Guirakhoo et al., J. Virol. 74:5477–5485, 2000). In this paper, we describe construction of three additional YF/DEN chimeras using premembrane (prM) and envelope (E) genes of wild-type (WT) clinical isolates: DEN1 (strain PUO359, isolated in 1980 in Thailand), DEN3 (strain PaH881/88, isolated in 1988 in Thailand), and DEN4 (strain 1228, isolated in 1978 in Indonesia). These chimeric viruses (YF/DEN1, YF/DEN3, and YF/DEN4) replicated to ∼7.5 log10 PFU/ml in Vero cells, were not neurovirulent in 3- to 4-week-old ICR mice inoculated by the intracerebral route, and were immunogenic in monkeys. All rhesus monkeys inoculated subcutaneously with one dose of these chimeric viruses (as monovalent or tetravalent formulation) developed viremia with magnitudes similar to that of the YF 17D vaccine strain (YF-VAX) but significantly lower than those of their parent WT viruses. Eight of nine monkeys inoculated with monovalent YF/DEN1 -3, or -4 vaccine and six of six monkeys inoculated with tetravalent YF/DEN1-4 vaccine seroconverted after a single dose. When monkeys were boosted with a tetravalent YF/DEN1-4 dose 6 months later, four of nine monkeys in the monovalent YF/DEN groups developed low levels of viremia, whereas no viremia was detected in any animals previously inoculated with either YF/DEN1-4 vaccine or WT DEN virus. An anamnestic response was observed in all monkeys after the second dose. No statistically significant difference in levels of neutralizing antibodies was observed between YF virus-immune and nonimmune monkeys which received the tetravalent YF/DEN1-4 vaccine or between tetravalent YF/DEN1-4-immune and nonimmune monkeys which received the YF-VAX. However, preimmune monkeys developed either no detectable viremia or a level of viremia lower than that in nonimmune controls. This is the first recombinant tetravalent dengue vaccine successfully evaluated in nonhuman primates.

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Comparison of three rocky mountain spotted fever vaccines

Journal of Clinical Microbiology ◽

10.1128/jcm.2.4.300-304.1975 ◽

1975 ◽

Vol 2 (4) ◽

pp. 300-304

Author(s):

R H Kenyon ◽

L S Sammons ◽

C E Pedersen

Keyword(s):

Chicken Embryo ◽

Rhesus Monkeys ◽

Protective Efficacy ◽

Spotted Fever ◽

Rocky Mountain ◽

Embryo Cell ◽

Yolk Sac ◽

Rocky Mountain Spotted Fever ◽

Duck Embryo ◽

Chicken Embryo Cell

Growth of Rocky Mountain spotted fever (RMSF) rickettsiae in duck embryo cell (DEC) cultures and chicken embryo cell (CEC) cultures was evaluated. Experimental lots of duck embryo cell- and chicken embryo cell-grown Rocky Mountain spotted fever vaccines and a commercial lot of yolk sac-grown vaccine were compared for protective efficacy in rhesus monkeys. Incidence and magnitude of antibody response, febrile response, and rickettsemia, as well as incidence of fatalities, suggested that both cell culture-derived vaccines were more immunogenic than the yolk sac-grown vaccine.

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