Texas A&M Professor Works with NIH-Supported Scientists to Elicit Broadly Neutralizing HIV Antibodies
Posted July 26, 2017
Dr. Michael Criscitiello
A team of scientists including Texas A&M College of Veterinary
Medicine & Biomedical Sciences (CVM) associate professor of
immunology Dr. Michael Criscitiello have achieved a significant
step forward in HIV research, eliciting broadly neutralizing
antibodies (bNAbs) to the virus by immunizing calves.
The National Institutes of Health (NIH)-supported scientists
reported the findings in a paper published online July 20 in the
academic journal Nature. Those findings offer insights for
HIV vaccine design and support further study of modified bovine
antibodies as HIV therapeutics or prevention tools in humans.
Researchers have observed that about 10-20 percent of people
living with HIV naturally develop neutralizing antibodies to the
virus, but usually only after nearly two years of infection. These
neutralizing antibodies have been shown in the laboratory to stop
most HIV strains from infecting human cells and to protect animal
models from infection.
However, scientists have so far been unsuccessful in prompting
the human immune system to produce these antibodies through
immunization. Further, while bNAbs isolated from people with HIV
infection have demonstrated promise in primate studies and have
entered human studies for HIV prevention and treatment, questions
remain about whether effective antibodies could be produced rapidly
and at a scale suitable for widespread distribution.
The researchers have determined that cattle may offer some help
in solving these problems.
“This work is exciting because a structural and genetic oddity
in cattle antibodies appears to allow them to easily and quickly
make effective antibodies to HIV that humans cannot,” Criscitiello
said. “The cattle antibodies may themselves be useful—with a few
While bovine neutralizing antibodies are not likely suitable for
clinical use in humans in their current form, exploring this rapid
production may help answer important research questions.
“From the early days of the epidemic, we have recognized that
HIV is very good at evading immunity, so exceptional immune systems
that naturally produce broadly neutralizing antibodies to HIV are
of great interest—whether they belong to humans or cattle,” said
Dr. Anthony S. Fauci, NIAID director.
“We never dealt with the entire HIV virus here (at Texas
A&M), but the cattle received immunizations containing a
protein designed to mimic a surface protein on HIV,” said
Criscitiello, who coordinated the A&M efforts with Scripps,
managed the animal work, and analyzed the antibody
While no one knows definitively why these powerful antibodies
evolved in cattle, one theory holds that the animals’ long HCDR3
loops are tied to their extensive gastrointestinal systems. Cattle
and other ruminant animals have multi-chambered stomachs and a
robust population of bacteria in their digestive tracts to help
break down a diet of tough grasses. However, these bacteria can
pose an infection risk if they escape the gut, so cattle with a
versatile mechanism for producing potent antibodies would greatly
benefit from the increased protection.
“A minority of people living with HIV produce neutralizing
antibodies, but only after a significant period of infection, at
which point virus in their body has already evolved to resist these
defenses,” said Dennis R. Burton, Ph.D., a lead author on the
study, director of the NIH’s Center for HIV/AIDS Vaccine Immunology
and Immunogen Discovery and scientific director of the IAVI
Neutralizing Antibody Consortium at the Scripps Research Institute.
“Unlike human antibodies, cattle antibodies are more likely to bear
unique features and gain an edge over complicated HIV
Further study on how this mechanism contributed to the
elicitation of bNAbs to HIV in cattle may inspire novel approaches
to HIV vaccine development.
“HIV is a human virus,” said Devin Sok, a study leader and IAVI
collaborator at the Scripps Research Institute, “but researchers
can certainly learn from immune responses across the animal
Researchers may also explore mimicking or modifying the potent
isolated bNAb, or those like it, to develop antibody-based HIV
therapeutics and prevention tools, as well as treatments for other
pathogens that have evolved to avoid human antibody responses.
Because the current research indicates that the bovine immune
system may typically work quickly to produce effective antibodies
against difficult pathogens such as HIV, immunizing cattle and
discovering such antibodies may become a useful approach to ensure
these tools are readily accessible.
To read the full report in Nature, visit
, and to see the full press release, visit the National Institute
of Allergy and Infectious Diseases website at
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