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Discovery may aid malaria vaccine development

Malaria parasite infecting

a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers say they have made a major advance in the quest toward a viable malaria vaccine—by uncovering a strategy the immune system employs to protect against malaria infection.

The team discovered how antibodies work in partnership with complement proteins to block Plasmodium falciparum infection.

And they believe this finding will aid the development of vaccine candidates that are already under investigation.

“We have known that antibodies on their own are not highly effective at blocking malaria, so they must be getting help from other parts of the immune system,” said James Beeson, MBBS, PhD, of the Burnet Institute in Melbourne, Victoria, Australia.

“This new research provides evidence that complement plays a key role in antibody-mediated immunity to blood-stage replication of Plasmodium falciparum malaria in humans.”

Dr Beeson and his colleagues described their research in Immunity.

The team found that acquired and vaccine-induced human antibodies recruited complement to block red blood cell infection and blood-stage replication of P falciparum.

Without complement, many of the antibodies were not functional, and P falciparum merozoites invaded red blood cells. But when the antibodies interacted with complement factors, they were able to prevent invasion and lyse merozoites.

Further investigation revealed that inhibitory activity was mediated predominately by C1q fixation, and merozoite surface proteins (MSPs) 1 and 2 were major targets of antibody-mediated complement-dependent (Ab-C’) inhibition.

To examine the importance of antibody-mediated complement fixation in acquired immunity to malaria, the researchers tested antibodies for C1q fixation in 206 children (ages 5 to 14) living in a malaria-endemic region.

This revealed that complement fixation was strongly associated with protection from clinical malaria and high-density parasitemia.

The researchers also investigated whether Ab-C′ inhibitory activity could be induced by human immunization with a candidate MSP vaccine. They studied 10 immunoglobulin G (IgG) samples from a phase 1 trial of the MSP2-C1 vaccine.

Eight of the IgG samples showed substantial inhibition in normal serum, but not in heat-inactivated serum, which suggests vaccination induced Ab-C’ inhibition. The researchers did not observe inhibition in IgG from pre-vaccinated individuals or placebo-vaccinated samples.

The team said this suggests that MSP2 antibodies induced by vaccination can inhibit P falciparum invasion via Ab-C’ inhibition.

“We have shown that it is possible to effectively generate this protective immune response by immunizing humans with a candidate vaccine,” Dr Beeson said, noting that this “may prove a valuable strategy to prevent the devastating effects of malaria.”

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Malaria parasite infecting

a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers say they have made a major advance in the quest toward a viable malaria vaccine—by uncovering a strategy the immune system employs to protect against malaria infection.

The team discovered how antibodies work in partnership with complement proteins to block Plasmodium falciparum infection.

And they believe this finding will aid the development of vaccine candidates that are already under investigation.

“We have known that antibodies on their own are not highly effective at blocking malaria, so they must be getting help from other parts of the immune system,” said James Beeson, MBBS, PhD, of the Burnet Institute in Melbourne, Victoria, Australia.

“This new research provides evidence that complement plays a key role in antibody-mediated immunity to blood-stage replication of Plasmodium falciparum malaria in humans.”

Dr Beeson and his colleagues described their research in Immunity.

The team found that acquired and vaccine-induced human antibodies recruited complement to block red blood cell infection and blood-stage replication of P falciparum.

Without complement, many of the antibodies were not functional, and P falciparum merozoites invaded red blood cells. But when the antibodies interacted with complement factors, they were able to prevent invasion and lyse merozoites.

Further investigation revealed that inhibitory activity was mediated predominately by C1q fixation, and merozoite surface proteins (MSPs) 1 and 2 were major targets of antibody-mediated complement-dependent (Ab-C’) inhibition.

To examine the importance of antibody-mediated complement fixation in acquired immunity to malaria, the researchers tested antibodies for C1q fixation in 206 children (ages 5 to 14) living in a malaria-endemic region.

This revealed that complement fixation was strongly associated with protection from clinical malaria and high-density parasitemia.

The researchers also investigated whether Ab-C′ inhibitory activity could be induced by human immunization with a candidate MSP vaccine. They studied 10 immunoglobulin G (IgG) samples from a phase 1 trial of the MSP2-C1 vaccine.

Eight of the IgG samples showed substantial inhibition in normal serum, but not in heat-inactivated serum, which suggests vaccination induced Ab-C’ inhibition. The researchers did not observe inhibition in IgG from pre-vaccinated individuals or placebo-vaccinated samples.

The team said this suggests that MSP2 antibodies induced by vaccination can inhibit P falciparum invasion via Ab-C’ inhibition.

“We have shown that it is possible to effectively generate this protective immune response by immunizing humans with a candidate vaccine,” Dr Beeson said, noting that this “may prove a valuable strategy to prevent the devastating effects of malaria.”

Malaria parasite infecting

a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Researchers say they have made a major advance in the quest toward a viable malaria vaccine—by uncovering a strategy the immune system employs to protect against malaria infection.

The team discovered how antibodies work in partnership with complement proteins to block Plasmodium falciparum infection.

And they believe this finding will aid the development of vaccine candidates that are already under investigation.

“We have known that antibodies on their own are not highly effective at blocking malaria, so they must be getting help from other parts of the immune system,” said James Beeson, MBBS, PhD, of the Burnet Institute in Melbourne, Victoria, Australia.

“This new research provides evidence that complement plays a key role in antibody-mediated immunity to blood-stage replication of Plasmodium falciparum malaria in humans.”

Dr Beeson and his colleagues described their research in Immunity.

The team found that acquired and vaccine-induced human antibodies recruited complement to block red blood cell infection and blood-stage replication of P falciparum.

Without complement, many of the antibodies were not functional, and P falciparum merozoites invaded red blood cells. But when the antibodies interacted with complement factors, they were able to prevent invasion and lyse merozoites.

Further investigation revealed that inhibitory activity was mediated predominately by C1q fixation, and merozoite surface proteins (MSPs) 1 and 2 were major targets of antibody-mediated complement-dependent (Ab-C’) inhibition.

To examine the importance of antibody-mediated complement fixation in acquired immunity to malaria, the researchers tested antibodies for C1q fixation in 206 children (ages 5 to 14) living in a malaria-endemic region.

This revealed that complement fixation was strongly associated with protection from clinical malaria and high-density parasitemia.

The researchers also investigated whether Ab-C′ inhibitory activity could be induced by human immunization with a candidate MSP vaccine. They studied 10 immunoglobulin G (IgG) samples from a phase 1 trial of the MSP2-C1 vaccine.

Eight of the IgG samples showed substantial inhibition in normal serum, but not in heat-inactivated serum, which suggests vaccination induced Ab-C’ inhibition. The researchers did not observe inhibition in IgG from pre-vaccinated individuals or placebo-vaccinated samples.

The team said this suggests that MSP2 antibodies induced by vaccination can inhibit P falciparum invasion via Ab-C’ inhibition.

“We have shown that it is possible to effectively generate this protective immune response by immunizing humans with a candidate vaccine,” Dr Beeson said, noting that this “may prove a valuable strategy to prevent the devastating effects of malaria.”

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