Pull to refresh
Logo
Daily Brief
Following Why Ranks Sign Up
The race to a 75% effective malaria vaccine

The race to a 75% effective malaria vaccine

New Capabilities

Scientists discover new antibody class that could unlock next-generation protection

March 7th, 2025: Uganda Launches Largest R21 Rollout

Overview

NIH researchers discovered a new class of antibodies that attack malaria parasites at a never-before-targeted site. The antibody MAD21-101 protected four out of five mice from infection, working differently than existing vaccines by binding to a cryptic protein fragment exposed only after the parasite undergoes pyroglutamylation, a specific chemical transformation. This opens a fresh avenue in the decades-long hunt for a highly effective malaria vaccine.

This matters because malaria killed 610,000 people in 2024, mostly African children under five. Two WHO-approved vaccines now reach 75% efficacy, meeting a goal set in 2013, but funding gaps hamper their rollout. The new antibody class could complement these vaccines or lead to monoclonal antibody treatments that provide immediate, long-lasting protection without multiple doses.

Play on this story Voices Debate Predict

Key Indicators

610,000
Global malaria deaths in 2024
95% occurred in Africa, 76% were children under 5
77%
Peak efficacy of R21 vaccine
First to meet WHO's 75% efficacy target set in 2013
100M+
Annual R21 production capacity
Scaling to 200M doses, priced at $4 per dose
16,000+
Malaria parasite strains analyzed
New antibody epitope conserved across nearly all strains

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

Sign up to generate historical perspectives on this story.

Log in Sign Up

Play

Exploring all sides of a story is often best achieved with Play.

Log in to play. Track your picks, climb the leaderboards. Log in Sign Up
Predict 4 ways this could play out. Contrarian picks score more — points lock when the scenario resolves. Log in to play
Connections Sixteen names from the news. Find the four hidden groups of four. Log in to play

People Involved

Robert A. Seder
Robert A. Seder
Leading MAD21-101 antibody research and monoclonal antibody trials
 Adrian V. S. Hill
Adrian V. S. Hill
Led development of R21/Matrix-M, the first vaccine to hit 75% efficacy
 Brandon DeKosky
Brandon DeKosky
Engineering improved malaria antibodies using machine learning platforms

Organizations Involved

National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Federal Research Agency
Published MAD21-101 discovery; conducting monoclonal antibody trials

Federal agency conducting and supporting research on infectious diseases, including malaria vaccine development.
World Health Organization
World Health Organization
UN specialized agency
Set 75% efficacy target; approved two vaccines for rollout

UN agency coordinating global health responses and setting vaccine efficacy targets.
Jenner Institute, University of Oxford
Jenner Institute, University of Oxford
Academic Research Institute
Developed R21/Matrix-M vaccine, now in mass production

Oxford vaccine research center that developed the first malaria vaccine to reach 75% efficacy.
Bill & Melinda Gates Foundation
Bill & Melinda Gates Foundation
Private Foundation
Pledged $912M for 2026-2028; aims to eradicate malaria by 2045

Largest private funder of malaria research and vaccine development globally.

Timeline

1973 March 2025

13 events Latest: March 7th, 2025 · 1 year ago Showing 8 of 13
Tap a bar to jump to that date

  1. Uganda Launches Largest R21 Rollout

    Latest Implementation

    2.3 million doses distributed to 105 districts, Africa's biggest deployment.

  2. NIH Discovers MAD21-101 Antibody Class

    Research Milestone

    Novel antibodies target cryptic pGlu-CSP epitope, opening new vaccine avenue.

  3. WHO Recommends R21 Vaccine

    Regulatory

    Second malaria vaccine approved, with 100M annual production capacity.

  4. Ghana Approves R21 Vaccine

    Regulatory

    First country to grant regulatory clearance for R21/Matrix-M.

  5. L9LS Shows 77% Protection in Children

    Clinical Trial

    Improved monoclonal antibody protects African children with single subcutaneous injection.

  6. WHO Recommends RTS,S Vaccine

    Regulatory

    First malaria vaccine approved for widespread use after decades of development.

  7. First Monoclonal Antibody Prevents Malaria

    Research Milestone

    NIH's CIS43LS shows 88% protection in humans, opening antibody-based prevention path.

  8. R21 Hits 77% Efficacy

    Clinical Trial

    Oxford's R21/Matrix-M becomes first vaccine to meet WHO's 75% efficacy goal.

  9. RTS,S Receives Regulatory Review

    Regulatory

    European Medicines Agency favorably reviews RTS,S, first malaria vaccine to reach this stage.

  10. WHO Sets 75% Efficacy Target

    Policy

    Malaria Vaccine Technology Roadmap sets goal for vaccines with 75%+ efficacy by 2030.

  11. First RTS,S Trial Shows Promise

    Clinical Trial

    Mozambique trial proves RTS,S safe and helps prevent malaria in young children.

  12. RTS,S Antigen Developed

    Research Milestone

    GlaxoSmithKline and Walter Reed Army Institute create CSP-based antigen.

  13. First Human Malaria Vaccine Trial

    Research Milestone

    Volunteer protected against malaria using X-irradiated sporozoites, proving vaccine concept works.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

1935-1955

Polio Vaccine Development (1935-1955)

Multiple research teams pursued polio vaccines through competing approaches—inactivated virus (Salk) and live attenuated virus (Sabin). Early trials with improperly inactivated virus caused infections, creating public fear. Salk's rigorous safety testing and a massive 1954 field trial with 1.8 million children proved efficacy, leading to 1955 approval. The Sabin oral vaccine followed in 1961, offering easier delivery.

Then

Polio cases in the U.S. dropped from 35,000 annually in the 1950s to less than 100 by 1965.

Now

Global polio cases fell 99.9%, with eradication efforts ongoing in remaining endemic countries.

Why this matters now

Like polio, malaria vaccine development required decades of iterative research, competing approaches (subunit vs. whole sporozoite vs. antibody), and eventually multiple complementary tools rather than a single perfect solution.

2010-present

HIV Monoclonal Antibody Research (2010-Present)

Researchers isolated broadly neutralizing antibodies from rare HIV patients whose immune systems naturally produce them. These antibodies target conserved viral sites less prone to mutation. Clinical trials demonstrated that antibodies like VRC01 and 3BNC117 could suppress viral load and prevent infection in animal models, but challenges with manufacturing, delivery, and viral escape limited their deployment as standalone prevention.

Then

Antibodies proved protective in trials but required high doses and frequent administration.

Now

Focus shifted to combining antibodies with vaccines or using them as templates for vaccine design, informing next-generation vaccine strategies.

Why this matters now

The MAD21-101 discovery parallels HIV antibody research: identifying conserved epitopes less likely to mutate, then using those insights to design better vaccines or deploy antibodies as seasonal prevention tools.

1967-1980

Smallpox Eradication Campaign (1967-1980)

WHO launched an intensified smallpox eradication program using an existing vaccine, ring vaccination strategies, and surveillance systems. The campaign required massive coordination across countries, training thousands of health workers, and reaching remote populations with cold chain logistics. The last natural case occurred in Somalia in 1977, and WHO declared eradication in 1980.

Then

Cases dropped from millions annually in the 1960s to zero by 1977 through coordinated global effort.

Now

Smallpox remains the only human disease eradicated globally, saving an estimated 5 million lives annually.

Why this matters now

Malaria elimination faces similar challenges: having effective vaccines is necessary but insufficient without health system infrastructure, funding, and coordinated deployment reaching the populations at highest risk in sub-Saharan Africa.

Sources

(12)
+6
National Institutes of Health Science World Health Organization University of Oxford Nature New England Journal of Medicine Journal of Clinical Investigation World Health Organization World Health Organization Nature Communications National Institutes of Health University of Oxford