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Os principais obstáculos científicos no desenvolvimento de vacinas eficazes contra HIV e SARS-CoV-2 : passado, presente e futuro
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Advisor(s)
Abstract(s)
Após a descoberta do HIV como agente responsável pela SIDA, o desenvolvimento de uma
vacina segura e eficaz tornou-se uma prioridade de saúde global. No entanto, o progresso tem
sido dificultado principalmente pela extensa variabilidade genética do HIV e pela
compreensão limitada das respostas imunitárias necessárias para proteger contra a
transmissão e aquisição do vírus. Os protótipos de vacinas candidatas contra o HIV, que
induzem respostas imunitárias humorais e celulares, não conseguiram, até à data, proteger
contra a infeção ou reduzir as cargas virais após a infeção, em ensaios de eficácia clínica. No
entanto, o vasto conhecimento acumulado a partir destes estudos forneceu informações sobre
a biologia estrutural do vírus, o aparecimento de antigénios e novos sistemas de
administração de vacinas que, no futuro, poderão constituir uma vacina eficaz.
O SARS-CoV-2 surgiu a 11 de março de 2020 e, desde então, o mundo inteiro sofreu com a
pandemia da COVID-19. Dois anos após o seu aparecimento, várias plataformas de vacinas,
incluindo vírus inativados, vacinas à base de ácidos nucleicos (vacinas de mRNA e DNA),
vacinas baseadas em adenovírus e em proteínas, foram rapidamente desenvolvidas e
distribuídas, permitindo o controlo com sucesso da pandemia e a redução significativa do
risco de doença grave e morte associada à doença. No entanto, devido à sua rápida capacidade
de evolução, e o aparecimento de novas variantes, o vírus SARS-CoV-2 poderá nunca ser
erradicado, e a eficácia das vacinas desenvolvidas poderá ser comprometida.
Desta forma, os investigadores aplicaram os resultados obtidos com sucessos e fracassos de
abordagens anteriores em novos sistemas de vacinas que permitem o avanço na área em
direção ao desenvolvimento de vacinas globalmente eficazes contra o HIV e SARS-CoV-2.
Nesta monografia, foi realizada uma revisão bibliográfica, de modo a compreender a história
das várias iniciativas no desenvolvimento de vacinas contra ambos os vírus, destacando os
principais desafios e direções futuras.
After the discovery of HIV as the agent responsible for AIDS, the development of a safe and effective vaccine became a global health priority. However, progress has been mostly challenged by HIV's extensive genetic variability and by our limited understanding of the immune responses that protect us against both transmission and acquisition of the virus. Prototype HIV vaccines, which induce humoral and cellular immune responses, haven't been able to prevent infection or reduce viral loads after infection in clinical efficacy trials. However, the knowledge gathered from these studies has brought information about the structural biology of the virus, the appearance of antigens and new vaccine platforms that, in the future, could establish an effective vaccine. SARS-CoV-2 emerged on March 11th of 2020, and since then the entire world was affected by the COVID-19 pandemic. Two years after its appearance, several vaccine platforms, including inactivated viruses, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-based and protein-based vaccines, were quickly developed and distributed, allowing the successful control of the pandemic and the significant reduction in the risk of serious illness and death associated with the disease. However, due to its rapid ability to evolve and the emergence of new variants, the SARS-CoV-2 virus may never be eradicated, and the effectiveness of the vaccines developed may be compromised. Thus, researchers applied the results obtained from previous approaches into new vaccine platforms that allow the field to advance towards the development of globally effective vaccines against HIV and SARS-CoV-2. In this monography, a literature review was carried out in order to understand the history of the various vaccine development initiatives against both viruses, highlighting not only its main challenges, but also those that may be expected in the future.
After the discovery of HIV as the agent responsible for AIDS, the development of a safe and effective vaccine became a global health priority. However, progress has been mostly challenged by HIV's extensive genetic variability and by our limited understanding of the immune responses that protect us against both transmission and acquisition of the virus. Prototype HIV vaccines, which induce humoral and cellular immune responses, haven't been able to prevent infection or reduce viral loads after infection in clinical efficacy trials. However, the knowledge gathered from these studies has brought information about the structural biology of the virus, the appearance of antigens and new vaccine platforms that, in the future, could establish an effective vaccine. SARS-CoV-2 emerged on March 11th of 2020, and since then the entire world was affected by the COVID-19 pandemic. Two years after its appearance, several vaccine platforms, including inactivated viruses, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-based and protein-based vaccines, were quickly developed and distributed, allowing the successful control of the pandemic and the significant reduction in the risk of serious illness and death associated with the disease. However, due to its rapid ability to evolve and the emergence of new variants, the SARS-CoV-2 virus may never be eradicated, and the effectiveness of the vaccines developed may be compromised. Thus, researchers applied the results obtained from previous approaches into new vaccine platforms that allow the field to advance towards the development of globally effective vaccines against HIV and SARS-CoV-2. In this monography, a literature review was carried out in order to understand the history of the various vaccine development initiatives against both viruses, highlighting not only its main challenges, but also those that may be expected in the future.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
HIV SARS-CoV-2 Vacinação Diversidade genética Resposta imunitária Mestrado Integrado - 2023