Experimental mRNA HIV vaccine safe, shows promise in animals

Date:
December 9, 2021
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
An experimental HIV vaccine based on mRNA -- the same platform
technology used in two highly effective COVID-19 vaccines --
shows promise in mice and non-human primates, according to
scientists. Their results show that the novel vaccine was safe and
prompted desired antibody and cellular immune responses against
an HIV-like virus.



FULL STORY ========================================================================== [Abstract illustration, | Credit: (c) niphon / stock.adobe.com] Abstract illustration, mRNA (stock image).

Credit: (c) niphon / stock.adobe.com [Abstract illustration, | Credit:
(c) niphon / stock.adobe.com] Abstract illustration, mRNA (stock image).

Credit: (c) niphon / stock.adobe.com Close An experimental HIV vaccine
based on mRNA -- the same platform technology used in two highly effective COVID-19 vaccines -- shows promise in mice and non- human primates,
according to scientists at the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of Health.

Their results, published in Nature Medicine, show that the novel vaccine
was safe and prompted desired antibody and cellular immune responses
against an HIV-like virus. Rhesus macaques receiving a priming vaccine
followed by multiple booster inoculations had a 79% lower per-exposure
risk of infection by simian-human immunodeficiency virus (SHIV) compared
to unvaccinated animals.

The research was led by Paolo Lusso, M.D., Ph.D., of NIAID's Laboratory
of Immunoregulation, in collaboration with other NIAID scientists, investigators from Moderna, Inc. and colleagues at other institutions.


========================================================================== "Despite nearly four decades of effort by the global research community,
an effective vaccine to prevent HIV remains an elusive goal," said NIAID Director Anthony S. Fauci, M.D., chief of the Laboratory and a paper
co-author. "This experimental mRNA vaccine combines several features that
may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach." The experimental vaccine works like
mRNA COVID-19 vaccines. However, instead of carrying mRNA instructions
for the coronavirus spike protein, the vaccine delivers coded instructions
for making two key HIV proteins, Env and Gag.

Muscle cells in an inoculated animal assemble these two proteins to
produce virus-like particles (VLPs) studded with numerous copies of
Env on their surface. Although they cannot cause infection or disease
because they lack the complete genetic code of HIV, these VLPs match
whole, infectious HIV in terms of stimulating suitable immune responses.

In studies with mice, two injections of the VLP-forming mRNA vaccine
induced neutralizing antibodies in all animals, the investigators
report. The Env proteins produced in the mice from the mRNA instructions closely resembled those in the whole virus, an improvement over previous experimental HIV vaccines. "The display of multiple copies of authentic
HIV envelope protein on each VLP is one of the special features of our
platform that closely mimics natural infection and may have played a
role in eliciting the desired immune responses," said Dr. Lusso.

The team then tested the Env-Gag VLP mRNA vaccine in macaques. The
details of the vaccine regimen differed among subgroups of vaccinated
animals but involved priming the immune system with a vaccine modified to optimize antibody creation. The prime was followed by multiple booster inoculations delivered over the course of a year. The boost vaccines
contained Gag mRNA and Env mRNA from two HIV clades other than the one
used in the prime vaccine. The investigators used multiple virus variants
to preferentially activate antibodies against the more conserved "shared" regions of the Env -- the target of broadly neutralizing antibodies --
rather than the more variable regions that differ in each virus strain.

Although the doses of mRNA delivered were high, the vaccine was well
tolerated and produced only mild, temporary adverse effects in the
macaques, such as loss of appetite. By week 58, all vaccinated macaques
had developed measurable levels of neutralizing antibodies directed
against most strains in a test panel of 12 diverse HIV strains. In
addition to neutralizing antibodies, the VLP mRNA vaccine also induced
a robust helper T-cell response.

Beginning at week 60, immunized animals and a control group of unimmunized macaques were exposed weekly, via the rectal mucosa, to SHIV. Because
non-human primates are not susceptible to HIV-1, scientists use a
chimeric SHIV in experimental settings because that virus replicates
in macaques. After 13 weekly inoculations, two out of seven immunized
macaques remained uninfected.

The other immunized animals had an overall delay in infection, which
occurred, on average, after eight weeks. In contrast, unimmunized animals became infected on average after three weeks.

"We are now refining our vaccine protocol to improve the quality and
quantity of the VLPs produced. This may further increase vaccine efficacy
and thus lower the number of prime and boost inoculations needed to
produce a robust immune response. If confirmed safe and effective,
we plan to conduct a Phase 1 trial of this vaccine platform in healthy
adult volunteers," said Dr. Lusso.

========================================================================== Story Source: Materials provided by NIH/National_Institute_of_Allergy_and_Infectious Diseases. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Peng Zhang, Elisabeth Narayanan, Qingbo Liu, Yaroslav Tsybovsky,
Kristin
Boswell, Shilei Ding, Zonghui Hu, Dean Follmann, Yin Lin, Huiyi
Miao, Hana Schmeisser, Denise Rogers, Samantha Falcone, Sayda
M. Elbashir, Vladimir Presnyak, Kapil Bahl, Madhu Prabhakaran,
Xuejun Chen, Edward K.

Sarfo, David R. Ambrozak, Rajeev Gautam, Malcom A. Martin, Joanna
Swerczek, Richard Herbert, Deborah Weiss, Johnathan Misamore,
Giuseppe Ciaramella, Sunny Himansu, Guillaume Stewart-Jones,
Adrian McDermott, Richard A. Koup, John R. Mascola, Andre's Finzi,
Andrea Carfi, Anthony S.

Fauci, Paolo Lusso. A multiclade env-gag VLP mRNA vaccine elicits
tier- 2 HIV-1-neutralizing antibodies and reduces the risk of
heterologous SHIV infection in macaques. Nature Medicine, 2021;
DOI: 10.1038/s41591-021- 01574-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211209124236.htm

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