Unexpected antibody type found in people with malaria infections
UM School of Medicine finding may lead to new avenues of research for identifying vaccine targets or treatments

Date:
November 2, 2021
Source:
University of Maryland School of Medicine
Summary:
Malaria, a pathogen transmitted into blood by mosquitoes in
tropical climates, is typically thought of as a blood and liver
infection. However researchers have detected antibodies primarily
made in response to infections in the mucous membranes -- in such
areas as the lungs, intestines, or vagina -- in study participants
with malaria.



FULL STORY ========================================================================== Malaria, a pathogen transmitted into blood by mosquitoes in tropical
climates, is typically thought of as a blood and liver infection. However,
in a newly published study, researchers at the University of Maryland
School of Medicine (UMSOM) have detected antibodies primarily made in
response to infections in the mucous membranes -- in such areas as the
lungs, intestines, or vagina -- in study participants with malaria.


==========================================================================
The researchers say that their unexpected finding provides new insight
into how the human body responds to malaria infection and may ultimately
help to identify new ways to treat malaria or develop vaccines.

The study was published on September 13 in NPJ Vaccines.

More than 400,000 people die each year of malaria infections, with
more than two-thirds of these deaths in children under 5 years old,
according to the World Health Organization (WHO). In early October 2021,
the WHO recommended widespread use of a new malaria vaccine in children
who live in regions with moderate to higher malaria transmission rates,
the first human vaccine to be recommended for a parasite infection. While
the vaccine would prevent millions of infections and save thousands
of lives, the researchers are actively pursuing the next generation of
malaria vaccines that may be even more effective.

"We've made progress in treating and preventing deaths due to malaria infections, but progress has plateaued, and we need new ideas," said
pediatric infectious disease physician and study author Andrea Berry,
MD, Associate Professor of Pediatrics at UMSOM and scientist at UMSOM's
Center for Vaccine Development and Global Health (CVD). "Not much had
been done to study IgA antibodies in malaria infections, because people
had not thought that they were important. Yet, because we were not
looking for them, we may have missed a whole avenue of research that
we can now explore." The body's immune system creates different kinds
of antibodies to help clear infections and to prevent reinfection. In
an earlier small study, the research team was studying other antibody
responses in patients with malaria infection.

While they detected the IgM antibody, which appears early in many
infections, along with IgG, which is the most abundant antibody, they
also found IgA antibodies. Researchers decided to follow up with a new
study to examine more samples to confirm what they had observed and to
study additional groups of people.



==========================================================================
For the new study, the research team looked at antibodies collected from
the blood of 54 adult research participants after being infected with
malaria in the laboratory -- either through an IV inserted directly
into the blood or through mosquito bites. They also examined samples
of blood taken from 47 children living in Mali, West Africa, who were
enrolled in a malaria vaccine trial and acquired malaria during the study period. Researchers detected high levels of IgA antibodies in the adult participants infected with malaria. In addition, 10 of the children had
levels of IgA antibodies similar to those of the adults tested.

"We do not know what triggers the IgA antibodies to develop, but we
think it happens early in a malaria infection," said Dr. Berry. "Some
people think that the response might happen when the mosquito injects
the parasite into the skin.

Interestingly, some of our participants were not bitten by mosquitoes
because their malaria infection was delivered intravenously, so there
are probably additional triggers for IgA development." Now, she said, determining why the children did not universally have high levels of IgA
will give researchers more of an understanding of how malaria infections
affect the body.

"There are several possible explanations for this difference between the
adults and the children," said Dr. Berry. "Perhaps, children's immune
systems respond differently to the parasite than adults do, or it is
possible that IgA antibodies are only created during the first malaria infection." She explained that in the adult participants, researchers
knew that they received their first infection, but whether the children
had been previously infected was unknown.

The timing of the infection and sample collection was uniform among
the adult study participants, but not with the children, because their
malaria infections were coincidental during the study.

Dr. Berry said they can now test to see if IgA antibodies prevent malaria parasites from going into the liver or red blood cells. They can also investigate which proteins in malaria these IgA antibodies target and
whether they would be good candidates to use in a vaccine.

"Even with medical advances, malaria remains one of the leading causes
of death in developing countries," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John
Z. and Akiko K.

Bowers Distinguished Professor, and Dean, UMSOM. "Getting back to basics
and exploring unknown fundamental mechanisms behind the body's response
to malaria infection may be the key to revealing new ways to prevent and
treat this devastating disease." This work was funded by the National Institute of Allergy and Infectious Diseases (grants U19AI065683,
N01AI25461, R44AI058375, R44AI055229, K23AI125720, U19AI110820,
U01AI110852, R01AE141900, R01AI067954, R01AI095916, 19AI089686 and
contracts HSN272201300022I, HHSN272201500002C, 2R44AI058375- 06A1), the
Fogarty International Center of the NIH (D43TW001589), the Doris Duke Charitable Foundation, Howard Hughes Medical Institute, the University
of Maryland, the National Center for Advancing Translational Sciences (1UL1TR003098), Sanaria, Inc., the Geneva Foundation (V-12VAXHFRS-03), the Medical Technology Enterprise Consortium (MTEC-17-01), Pfizer (C4591001)
and the Joint Warfighter Medical Research Program (W81XWH-JW14843), a
Doris Duke Clinical Scientist Development Award, and the National Heart,
Lung, and Blood Institute (K01HL140285-01A1).

Two of the study authors work for Sanaria, Inc. Sanaria raised the
laboratory mosquitos and manufactured the malaria given to patients intravenously.

========================================================================== Story Source: Materials provided by
University_of_Maryland_School_of_Medicine. Original written by Vanessa
McMains. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Andrea A. Berry, Joshua M. Obiero, Mark A. Travassos, Amed Ouattara,
Drissa Coulibaly, Matthew Adams, Rafael Ramiro de Assis, Aarti
Jain, Omid Taghavian, Andrew Sy, Rie Nakajima, Algis Jasinskas,
Matthew B. Laurens, Shannon Takala-Harrison, Bourema Kouriba,
Abdoulaye K. Kone, Ogobara K.

Doumbo, B. Kim Lee Sim, Stephen L. Hoffman, Christopher
V. Plowe, Mahamadou A. Thera, Philip L. Felgner, Kirsten
E. Lyke. Immunoprofiles associated with controlled human malaria
infection and naturally acquired immunity identify a shared IgA
pre-erythrocytic immunoproteome. npj Vaccines, 2021; 6 (1) DOI:
10.1038/s41541-021-00363-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211102180524.htm

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