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Results & Discussion

Qazi Laeeque Ahmed

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28.Results All monkeys were seronegative for prior dengue infection at baseline by ELISA and anti-DENV-1 PRNT50. ELISAs (for IgM & IgG) and PRNT50 were performed on days 0. 14. Two groups of seven monkeys received either 10 ng of AMTphotoinactivated DENV-1 (vaccine group) plus Alhydrogel or PBS plus Alhydrogel (control group) on study days 0. and 62. and 28. 2 . 14.

28 vaccinated animals on the day As a group. One control animal had a detectable IgM on the day of challenge that had All monkeys were challenged with DENV-1 on study day 132. IgMchallenge) in 2/7in 5/7 by days was subsequently detectable in 7/7 day was detectable animals. No control animals had ELISAs were performed on days 0. IgM 14 and 28 before declining to 2/7 on 62. vaccinated animals by day 141 and persisted in 6/7 by day 160. Anti-DENV-1 IgM was undetectable in & 62. control animals mounted a more rapid IgM response. but a confirmatory PRNT50 was negative with no evidence of prior dengue virus infection. with detectable IgM titersbecamethis study period. of challenge but during detectable by days 138 (day 6 postdetectable IgM in 6/6 by day 139 and persisting through day 160. 14. not been present on day 62. Among vaccinated animals. 3 .1-Mean IgM ELISA OD following vaccination on days 0–28 and following viral challenge on day 132.

detectable in 6/72/6 control animals by Among the vaccinated to prior IgG was the 7/7 on days 28 and 62. No control animals had Mean IgG OD values detectable in the vaccine group. with an amnesticrapidly during challenge.exposure. 14. All monkeys were challenged with DENV-1 on study day 132. and in tenth post-challenge day but in 6/6 by days 14 and 28 post-challenge. challenge. 4 . declined at days Anti-DENV-1 IgG during this study 4/7 vaccinated animals at the time of detectable IgG titerswas were higher inperiod.2-Mean IgG ELISA OD following vaccination on days 0–28 and following viral challenge on day 132. and then rose response leading to detectable IgG with by amnestic post-challenge. and 62. consistent in 7/7an the 62 until 132. IgG was detectable only in animals by day 14 eighth dayresponse animals. ELISAs were performed on days 0. 28.

Among vaccinated animals Neutralizing antibodies as assessed by PRNT50 were below the threshold of detection on day 14 but were detectable in all vaccinated animals on day 28 and day 62. 5 . Monkey # 5 in the control group was removed from the study prior to viral challenge.3-PRNT50 against DENV-1 following vaccination or PBS control PRNT50 were performed on days 0. 28. and 62. 14. No anti-DENV-1 neutralizing antibodies were detectable in control animals.

The mean days of viremia per animal were 3.4-DENV-1 virus detected by indirect IFA following vaccination Daily serum specimens drawn on the day of challenge and for 10 days post-challenge were assessed for viremia by indirect IFA.71 days/animal among vaccinated monkeys. 6 .67 days/animal among control monkeys and 0.

• The principal advantages of psoralens inactivation include their low toxicity and lack of conformational changes on viral epitopes. • Dengue-1 virus inactivated by 4′-aminomethyltrioxsalen (AMT) and UV-A is immunogenic in Aotus nancymaae and produces both an amnestic antibody response to in vivo challenge and a reduction in the days of viremia in vaccinated animals. Psoralen/UV-A inactivation of dengue viruses may be a useful method of vaccine candidate development. 7 .Discussion • The development of an effective dengue vaccine candidate has become a leading public health priority in recent years.

with these heterotypic antibodies enhancing the ability of dengue viruses to infect cells (ADE) via binding to the immunoglobulin FcR. 8 . • Incomplete protection from a dengue vaccine raises concerns for possible antibody-dependent enhancement of infection. • Any final dengue vaccine must be shown to have tetravalent and lasting protection prior to widespread human use. • Heterotypic antibodies to a prior infecting dengue serotype appear to contribute to the subsequent development of DHF.• Homotypic antibodies to an infecting serotype play a major role in the prevention of recurrent infection.

9 .The Aotus nancymaae nonhuman primate model has been previously used to evaluate DENV-1 and DENV-3 DNA vaccines encoding for viral premembrane/membrane (prM) and envelope (E) genes. These candidates have shown immunogenicity and reduced days of viremia compared with controls. although the magnitudes of reduction were smaller as compared to this study.

DENV-4 and tetravalent formulation. • Development and role of cell mediated immunity against DENV. 10 . DENV-3. • Testing of psoralen inactivated DENV-2. or non-alum adjuvants. alternate routes of administration.Areas to be Explored Further • Vaccinated monkeys did display protective responses to DENV-1 infection. but this protection was incomplete. Homotypic and heterotypic cell mediated immunity & cytokines production (TNF-α). Immunogenecity can be augmented through higher or greater numbers of doses.

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