scholarly journals HIV mRNA Vaccines—Progress and Future Paths

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 134
Author(s):  
Zekun Mu ◽  
Barton F. Haynes ◽  
Derek W. Cain

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

1998 ◽  
Vol 187 (4) ◽  
pp. 649-654 ◽  
Author(s):  
Peter Seiler ◽  
Marie-Anne Bründler ◽  
Christine Zimmermann ◽  
Doris Weibel ◽  
Michael Bruns ◽  
...  

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 102 PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV–glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 106 PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.


2005 ◽  
Vol 79 (10) ◽  
pp. 5988-5995 ◽  
Author(s):  
Rahnuma Wahid ◽  
Martin J. Cannon ◽  
Marie Chow

ABSTRACT The presence of poliovirus (PV)-specific CD4+ T cells in individuals vaccinated against polio has been shown, but CD8+ T-cell responses have not been described. Here, we functionally characterize the CD4+ T-cell response and show for the first time that dendritic cells and macrophages can stimulate PV-specific CD8+ T-cell responses in vitro from vaccinees. Both CD4+ T and CD8+ T cells secrete gamma interferon in response to PV antigens and are cytotoxic via the perforin/granzyme B-mediated pathway. Furthermore, the T cells also recognize and kill Sabin 1 vaccine-infected targets. The macrophage-stimulated CD4+ T and CD8+ T cells most likely represent memory T cells that persist for long periods in vaccinated individuals. Thus, immunity to PV vaccination involves not only an effective neutralizing antibody titer but also long-term CD4+ and CD8+ cytotoxic T-cell responses.


2005 ◽  
Vol 18 (4) ◽  
pp. 234-242 ◽  
Author(s):  
Silvia Garbelli ◽  
Stefania Mantovani ◽  
Belinda Palermo ◽  
Claudia Giachino

2004 ◽  
Vol 169 (12) ◽  
pp. 1322-1330 ◽  
Author(s):  
Frédéric Ebstein ◽  
Carole Sapede ◽  
Pierre-Joseph Royer ◽  
Marie Marcq ◽  
Catherine Ligeza-Poisson ◽  
...  

Author(s):  
Elena Sadovnikova ◽  
Xiaojiu Zhu ◽  
Shona M. Collins ◽  
Peter Beverley ◽  
Hans J. Stauss

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