HIV vaccines: The effect of the mode of action on the coexistence of HIV subtypes

Porco, Travis C.; Blower, Sally

doi:10.1080/08898480009525481

Cited by 29 publications

(23 citation statements)

References 33 publications

(23 reference statements)

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“…These analyses (14)(15)(16)(17)(18)(19)(20)(21)(22) have evaluated the consequences of vaccines that do not have the potential to cause AIDS. Here, we present a theoretical framework that enables us to model the effects of a mass vaccination campaign that uses a LAHV.…”

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confidence: 99%

“…and (ii) what impact would a mass vaccination campaign with a LAHV have on the annual AIDS death rate? We discuss the implications of our results for vaccine design, phase III clinical trials, and epidemic control strategies.Mathematical models of HIV vaccines have been used: (i) to calculate vaccine efficacy and vaccination coverage levels for eradicating HIV (using a prophylactic non-LAHV) (14-16), (ii) to design phase III trials (17-19), (iii) to evaluate the effect of changes in risk behavior on vaccination campaigns (15,20), and (iv) to determine the degree of vaccine-induced cross-immunity that would be necessary to control multiple subtypes (20)(21)(22). These analyses (14-22) have evaluated the consequences of vaccines that do not have the potential to cause AIDS.…”

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confidence: 99%

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Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety

Blower

Koelle

Kirschner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccineinduced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe. Live attenuated vaccines (due to their high protective efficacy, low cost, and simple immunization schedules) have been used successfully to control smallpox, polio, and measles epidemics (1, 2). Preliminary attempts have been made to develop a live attenuated HIV vaccine (LAHV) (3-6); however, the debate about the potential utility of developing LAHVs has been controversial, mainly due to concerns that have arisen about vaccine safety (3, 4, 7-9). The major safety concern is that even a very attenuated strain of HIV (if used as a LAHV) could actually cause AIDS in some fraction of vaccinated individuals (4, 5). Live attenuated polio vaccine has caused some cases of paralytic poliomyelitis (10), and any live attenuated vaccine has the potential to cause disease. Studies in macaques of the closely related simian immunodeficiency virus have shown that live attenuated strains can be highly effective in protecting against infection with the wild-type strain (4, 11), but that some macaques develop AIDS as a result of the attenuated strain (5, 12). Concern about the potential safety of LAHVs has been heightened by a recent report of the natural history of HIV infection in a cohort of gay men in Australia (13). Some of these men were infected with a naturally attenuated strain of HIV. Long-term follow-up studies of this cohort have shown that this strain of HIV, although attenuated, can cause immune deterioration (13). The design of a LAHV t...

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confidence: 99%

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confidence: 99%

Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety

Blower

Koelle

Kirschner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…The superscripts U and V indicate unvaccinated and vaccinated, respectively. This model is discussed in further detail in [81]. Fig.…”

Section: Transmission Models and Health Policymentioning

confidence: 98%

Predicting the Potential Public Health Impact of Disease-Modifying HIV Vaccines in South Africa: The Problem of Subtypes

Blower¹,

Bodine²,

Grovit-Ferbas³

2005

CDTID

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Current HIV vaccines in development appear unlikely to prevent infection, but could provide benefits by increasing survival; such vaccines are described as disease-modifying vaccines. We review the current status of vaccines and modeling vaccines. We also predict the impact that disease-modifying vaccines could have in South Africa, where multiple subtypes are co-circulating. We model transmissibility/fitness differences among subtypes. We used uncertainty analyses to model vaccines with four characteristics: (i) take, (ii) duration of immunity, (iii) reduction in transmissibility/fitness, and (iv) increase in survival. We reconstructed, and forecasted, the South African epidemic from 1940 to 2140 (assuming no vaccination). We predict that: (i) incidence will peak in 2014, decline, and stabilize, (ii) prevalence will continue to rise, and (iii) the AIDS death rate curve will peak in 2022. Our predictions show that (over the next 135 years) the epidemic in South Africa will switch from a predominantly Subtype C epidemic to an epidemic driven by other subtypes. We predict that the epidemic could remain unchanged, even with mass vaccination with a vaccine that is equally effective against all co-circulating subtypes. However, if the non-C subtypes are less (or equally) transmissible as Subtype C then disease-modifying vaccines could result in eradication. Thus, in countries where multiple-subtypes are co-circulating it is critical to realize that small biological differences among subtypes will have dramatic consequences for the effectiveness of HIV vaccination campaigns. A slight difference in fitness will determine whether a disease-modifying vaccine has almost no impact on the epidemic or can achieve eradication.

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“…The equilibrium fractions of susceptiblex 1 can be computed by setting equal to 0 the right hand side of (8) so that it can be expressed as function ofȳ 1 (20) into (19) we obtain thatȳ 1 must solve G(ȳ 1 ) = 1, where…”

Section: Existencementioning

confidence: 99%

“…Vaccination can destabilize the existing host-pathogen evolutionary equilibria, accelerate pathogen evolution and also lead to the emergence or dominance of a once-rare pathogen, a mechanism also known as strain replacement [8,6,7]. Vaccines differ for their mode of action; vaccines with differential effectiveness provide different degrees of protection against infection by the different strains of the pathogen and their efficacy has been extensively discussed in the literature [9,10,11,7].…”

Section: Introductionmentioning

confidence: 99%

Analysis of a vaccine model with cross-immunity: When can two competing infectious strains coexist?

Dorigatti

2011

Mathematical Biosciences

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We analyse here the Vaccine Model with Cross-Immunity proposed by Porco and Blower [1]. Porco and Blower[1] show that vaccination can shift the competitive balance in favour of a strain that, without vaccination, would be out-competed and that vaccination can also promote coexistence of different strains, something that normally is not expected [2]. Their results have been mainly obtained through numerical simulations, so that the conditions under which a shift in competitive balance or coexistence occurs have not been fully established.We give a rather complete description of its behavior, at least in terms of equilibria. We find the exact conditions under which vaccination may lead to a shift in competitive balance and show that, under these conditions, there always exist a range of vaccination rates under which a coexistence equilibrium exists. We also find that a coexistence equilibrium exists (and is unstable) in a 'bi-stability' region, where both 1 *Manuscript monomorphic equilibria are stable. This fact has been rarely observed in models of competition between pathogen strains.

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HIV vaccines: The effect of the mode of action on the coexistence of HIV subtypes

Cited by 29 publications

References 33 publications

Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety

Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety

Predicting the Potential Public Health Impact of Disease-Modifying HIV Vaccines in South Africa: The Problem of Subtypes

Analysis of a vaccine model with cross-immunity: When can two competing infectious strains coexist?

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