Current approaches to HIV vaccine development: a narrative review

ABSTRACT Given the complex biology of human immunodeficiency virus (HIV) and its remarkable capacity to evade host immune responses, HIV vaccine efficacy may benefit from the induction of both humoral and cellular immune responses of maximal breadth, potency, and longevity. Guided by this rationale, we set out to develop an immunization protocol aimed at maximizing the induction of anti-Envelope (anti-Env) antibodies and CD8+ T cells targeting non-Env epitopes in rhesus macaques (RMs). Our approach was to deliver the entire simian immunodeficiency virus (SIV) proteome by serial vaccinations. To that end, 12 RMs were vaccinated over 81 weeks with DNA, modified vaccinia Ankara (MVA), vesicular stomatitis virus (VSV), adenovirus type 5 (Ad5), rhesus monkey rhadinovirus (RRV), and DNA again. Both the RRV and the final DNA boosters delivered a near-full-length SIVmac239 genome capable of assembling noninfectious SIV particles and inducing T-cell responses against all nine SIV proteins. Compared to previous SIV vaccine trials, the present DNA-MVA-VSV-Ad5-RRV-DNA regimen resulted in comparable levels of Env-binding antibodies and SIV-specific CD8+ T-cells. Interestingly, one vaccinee developed low titers of neutralizing antibodies (NAbs) against SIVmac239, a tier 3 virus. Following repeated intrarectal marginal-dose challenges with SIVmac239, vaccinees were not protected from SIV acquisition but manifested partial control of viremia. Strikingly, the animal with the low-titer vaccine-induced anti-SIVmac239 NAb response acquired infection after the first SIVmac239 exposure. Collectively, these results highlight the difficulties in eliciting protective immunity against immunodeficiency virus infection. IMPORTANCE Our results are relevant to HIV vaccine development efforts because they suggest that increasing the number of booster immunizations or delivering additional viral antigens may not necessarily improve vaccine efficacy against immunodeficiency virus infection.

Download Full-text

Entamoeba Histolytica: Updates in Clinical Manifestation, Pathogenesis, and Vaccine Development

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/4601420 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 17

Author(s):

Micaella Kantor ◽

Anarella Abrantes ◽

Andrea Estevez ◽

Alan Schiller ◽

Jose Torrent ◽

...

Keyword(s):

Immune Response ◽

Entamoeba Histolytica ◽

Clinical Manifestation ◽

Vaccine Development ◽

Current Knowledge ◽

Developed Countries ◽

Narrative Review ◽

Amoebic Colitis ◽

Causes Of Mortality ◽

Disseminated Disease

Entamoeba histolyticais the responsible parasite of amoebiasis and remains one of the top three parasitic causes of mortality worldwide. With increased travel and emigration to developed countries, infection is becoming more common in nonendemic areas. Although the majority of individuals infected withE. histolyticaremain asymptomatic, some present with amoebic colitis and disseminated disease. As more is learned about its pathogenesis and the host’s immune response, the potential for developing a vaccine holds promise. This narrative review outlines the current knowledge regardingE. histolyticaandE. disparand insight in the development of a vaccine.

Download Full-text

HIV vaccine development

Annals of Ibadan Postgraduate Medicine ◽

10.4314/aipm.v3i2.39063 ◽

2007 ◽

Vol 3 (2) ◽

Author(s):

JA Idoko ◽

SO Isa

Keyword(s):

Vaccine Development ◽

Hiv Vaccine

Download Full-text

Exhausted B cells potential hurdle for HIV vaccine development

Inpharma Weekly ◽

10.2165/00128413-200816470-00019 ◽

2008 ◽

Vol &NA; (1647) ◽

pp. 5

Author(s):

&NA;

Keyword(s):

B Cells ◽

Vaccine Development ◽

Hiv Vaccine

Download Full-text

Genetically identical primate modelling systems for HIV vaccines

Reproduction Fertility and Development ◽

10.1071/rd98057 ◽

1998 ◽

Vol 10 (8) ◽

pp. 651 ◽

Cited By ~ 2

Author(s):

Stephen J. Kent ◽

Ian M. Lewis

Keyword(s):

Immune Responses ◽

Hiv Infection ◽

Vaccine Development ◽

Careful Consideration ◽

Hiv Vaccine ◽

Effective Vaccine ◽

Hiv Vaccines ◽

Major Step ◽

Immunodeficiency Virus ◽

Hiv 1

There is an urgent need for a safe and effective vaccine to prevent human immunodeficiency virus (HIV) infection. Several HIV vaccine candidates have shown promise, but many concerns regarding the safety and efficacy of current vaccines remain. A major hindrance in HIV vaccine development is a poor understanding of precisely what functions HIV vaccines are required to perform in order to protect humans from HIV-1. Only higher primates (i.e. macaques, chimpanzees and humans) are susceptible to HIV-1 or the closely related virus ‘simian immunodeficiency virus’. These species are outbred and there are remarkable genetic differences in both the immune responses to vaccines and their susceptibility to infection. The development of genetically identical macaques would be a major step towards dissecting what immune responses are required to protect from HIV infection. For example, live attenuated HIV-1 vaccines are likely to be highly efficacious, but will induce disease in a substantial proportion of recipients. Defining why a live attenuated vaccine is effective should allow safer vaccines to be developed, retaining only the immunologic properties of an effective vaccine. The reduction in ‘background genetic noise’ obtained by studying genetically identical primates would provide concise answers to critical HIV vaccine issues, by studying a minimal number of animals. Such an approach could potentially be employed in other diseases where non-human primates are the only available model. Small studies can be performed where identical twins are generated by embryo bisection; however, larger studies where multiple immune parameters are simultaneously evaluated would be facilitated by cloning technology. Despite the technical difficulties to be overcome, the potential gains in human health from the development of genetically identical non-human primates are worthy of careful consideration.

Download Full-text