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Antivirals and Vaccines: Molecular Research in Treatment and Prevention

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Dear Colleagues,

As the HIV, HCV and SARS-Cov-2 pandemics well illustrate, antivirals or vaccines have been crucial to control transmission, prevent disease progression and avert a very significant number of deaths caused by viral infections. However, vaccines are still not available for most virus infections and diseases including those caused by HIV and HCV. Likewise, a very limited number of drugs is currently available to treat deadly viral infections such as lower respiratory infections caused by RSV, influenza viruses and coronaviruses. Moreover, drug resistance is increasing in certain viruses such as HIV threatening the success obtained so far in controlling this pandemic. New and better antiviral drugs are in need to fight this global public health threat. This special issue of the International Journal of Molecular Sciences seeks to attract top level publications on the design, development and validation of new antivirals and vaccines to treat and prevent human viral diseases. We invite you to share with us your most insightful primary research work, reviews, and hypothesis on these important topics.

Prof. Dr. Nuno Taveira
Guest Editor

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Keywords

antivirals
antiviral drugs
broad-spectrum antivirals
neutralizing antibodies
drug targets and mechanism of action
drug resistance
antiviral vaccines
vaccine immunogens
immunogen design
mRNA vaccines
self-amplifying mRNA vaccines
vaccine adjuvants
animal models

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Research

19 pages, 5691 KiB

Open AccessArticle

Generation and Characterization of Recombinant Pseudorabies Virus Delivering African Swine Fever Virus CD2v and p54

by Jianhui Wei, Chuancheng Liu, Xinyan He, Bilal Abbas, Qi Chen, Zhaolong Li and Zhihua Feng

Int. J. Mol. Sci. 2024, 25(1), 335; https://doi.org/10.3390/ijms25010335 - 26 Dec 2023

Cited by 1 | Viewed by 888

Abstract

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections. Full article

(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)

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14 pages, 2773 KiB

Open AccessArticle

An HIV-1/HIV-2 Chimeric Envelope Glycoprotein Generates Binding and Neutralising Antibodies against HIV-1 and HIV-2 Isolates

by Nuno Taveira, Inês Figueiredo, Rita Calado, Francisco Martin, Inês Bártolo, José M. Marcelino, Pedro Borrego, Fernando Cardoso and Helena Barroso

Int. J. Mol. Sci. 2023, 24(10), 9077; https://doi.org/10.3390/ijms24109077 - 22 May 2023

Viewed by 1500

Abstract

The development of immunogens that elicit broadly reactive neutralising antibodies (bNAbs) is the highest priority for an HIV vaccine. We have shown that a prime-boost vaccination strategy with vaccinia virus expressing the envelope glycoprotein gp120 of HIV-2 and a polypeptide comprising the envelope regions C2, V3 and C3 elicits bNAbs against HIV-2. We hypothesised that a chimeric envelope gp120 containing the C2, V3 and C3 regions of HIV-2 and the remaining parts of HIV-1 would elicit a neutralising response against HIV-1 and HIV-2. This chimeric envelope was synthesised and expressed in vaccinia virus. Balb/c mice primed with the recombinant vaccinia virus and boosted with an HIV-2 C2V3C3 polypeptide or monomeric gp120 from a CRF01_AG HIV-1 isolate produced antibodies that neutralised >60% (serum dilution 1:40) of a primary HIV-2 isolate. Four out of nine mice also produced antibodies that neutralised at least one HIV-1 isolate. Neutralising epitope specificity was assessed using a panel of HIV-1 TRO.11 pseudoviruses with key neutralising epitopes disrupted by alanine substitution (N160A in V2; N278A in the CD4 binding site region; N332A in the high mannose patch). The neutralisation of the mutant pseudoviruses was reduced or abolished in one mouse, suggesting that neutralising antibodies target the three major neutralising epitopes in the HIV-1 envelope gp120. These results provide proof of concept for chimeric HIV-1/HIV-2 envelope glycoproteins as vaccine immunogens that can direct the antibody response against neutralising epitopes in the HIV-1 and HIV-2 surface glycoproteins. Full article

(This article belongs to the Special Issue Antivirals and Vaccines: Molecular Research in Treatment and Prevention)

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