Vaccine shows potential against deadly leptospirosis bacteria
A potential vaccine protects hamsters and mice against death caused by multiple Leptospira species, and prevents kidney colonization in mice

Date:
January 26, 2021
Source:
eLife
Summary:
Scientists have designed a single-dose universal vaccine that
could protect against the many forms of leptospirosis bacteria,
according to a new study.



FULL STORY ========================================================================== Scientists have designed a single-dose universal vaccine that could
protect against the many forms of leptospirosis bacteria, according to
a study published today in eLife.


==========================================================================
An effective vaccine would help prevent the life-threatening conditions
caused by leptospirosis, such as Weil's disease and lung haemorrhage,
which are fatal in 10% and 50% of cases, respectively.

Leptospirosis is caused by a diverse group of spirochetes called
leptospires. A broad range of mammals, including rats, harbour the
bacteria in their kidneys and release them into the environment through
their urine. Humans and animals can then get infected after coming into
contact with contaminated water or soil. In addition to having a major
impact on the health of vulnerable human populations, leptospirosis is
an economically important animal health problem, making it a significant
One Health challenge. This means that collaborative efforts are needed
across disciplines and sectors to improve public health outcomes against leptospirosis infection.

The Leptospira family of bacteria is made up of 64 species with 300
different varieties (called serovars). This makes developing a vaccine challenging, because researchers need to find a common feature of the
bacteria that will trigger an immune response.

"We have recently identified a novel protein called FcpA in the flagella
of Leptospira which enables it to move and penetrate human and animal
tissues," explains first author Elsio Wunder Jr, Associate Research
Scientist in Epidemiology (Microbial Diseases) at Yale School of Public
Health, Yale University, New Haven, US. "With this study, we wanted to
see whether using engineered Leptospira that lacks a functional FcpA
molecule has the potential for a vaccine that could provide major public
health benefit." The mutated FcpA Leptospira was tested as an attenuated vaccine -- a live vaccine that cannot cause disease. After the vaccine was given to hamsters and mice, it disseminated throughout the body before
being cleared within seven days in the hamsters and after two weeks in
the mice. No traces of the mutated Leptospira could be detected in kidney tissue or blood after this time point, showing that the attenuated vaccine
is cleared by the immune system before it results in disease or death.

To test whether the vaccine candidate could protect against all types of Leptospira infection, they tested a single dose of the mutant Leptospira
and compared this against heat-killed Leptospira to see whether they
could prevent infection and disease by a range of similar and different serovars.

Immunisation with the heat-killed vaccine gave partial protection
against similar serovars but not against different serovars of
Leptospira. By contrast, the attenuated vaccine (mutated Leptospira)
provided cross-protection against serovars belonging to three different
species of Leptospira, which encompass the majority of serovars of
importance to human and animal health.

Further analysis of the mice and hamsters after vaccination showed
that they generated antibodies that recognised a wide range of proteins
across the different species of Leptospira. Moreover, by studying the
antibody response in detail, the team identified 41 different proteins
that could be targets for future vaccines. The majority of these proteins
(70%) looked similar across all 13 disease-causing species of Leptospira studied, suggesting they are likely to be important to the microbes'
survival and would make effective future vaccine candidates.

"In this proof-of-concept study, we have shown that a universal
leptospirosis vaccine candidate can prevent both death and kidney
colonisation in animal models," concludes author Albert Ko, Department
Chair and Professor of Epidemiology (Microbial Diseases) at Yale
School of Public Health. "These findings take us one step closer to
achieving the holy grail for the field, which is an effective vaccine
that protects against the many Leptospira species and can be deployed
as a broad solution to the human and animal health challenge caused
by leptospirosis."

========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Elsio A Wunder, Haritha Adhikarla, Camila Hamond, Katharine A Owers
Bonner, Li Liang, Camila B Rodrigues, Vimla Bisht, Jarlath E Nally,
David P Alt, Mitermayer G Reis, Peter J Diggle, Philip L Felgner,
Albert Ko. A live attenuated-vaccine model confers cross-protective
immunity against different species of the Leptospira genus. eLife,
2021; 10 DOI: 10.7554/ eLife.64166 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/01/210126134026.htm

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