Vaccine development in the spotlight as WHO sets out roadmap to tackle meningitis

The organization, along with its partners, has published a global strategy to defeat meningitis. 

The roadmap sets the goal of reducing cases of vaccine-preventable bacterial meningitis by 50% and deaths by 70% by 2030, compared to a baseline of 2015. 

There are two key objectives for vaccines: firstly to increase availability of vaccines where they are needed most; and secondly to develop new vaccines to combat the disease.

Vaccine-preventable cases 

WHO goals

Eliminate bacterial meningitis epidemics
Reduce cases of vaccine-preventable bacterial meningitis by 50% and deaths by 70% (Vaccine-preventable bacterial meningitis refers to all acute bacterial meningitis caused by Nm, Spn, Hi and GBS whatever the serotype/group).
Reduce disability and improve quality of life after meningitis due to any cause

Meningitis is a life-threatening disease caused by inflammation of the membranes that surround the brain and spinal cord and is predominantly caused by infection with bacteria and viruses. 

Acute bacterial meningitis is one of the deadliest and most disabling forms of this illness; it can cause epidemics, lead to death within 24 hours and leave one in five people with lifelong disability after infection.

Many cases of and deaths from meningitis are vaccine-preventable, but progress in defeating meningitis lags behind other vaccine-preventable diseases, according to the WHO's roadmap.

The roadmap sets out strategies to tackle the main causes of acute bacterial meningitis: Neisseria meningitidis ((Nm), meningococcus), Streptococcus pneumoniae ((Spn), pneumococcus), Haemophilus influenzae (Hi) and Streptococcus agalactiae (group B Streptococcus (GBS)).

Nm, Spn, Hi: Increasing uptake

Several vaccines protect against meningitis, including meningococcal, Haemophilus influenzae type b (Hib) and pneumococcal vaccines. However, not all communities have access to these vaccines, and many countries are yet to introduce them into their national programmes. 

Enhanced efforts are needed to encourage all recommended immunization, especially in low- and middle-income countries where the burden of meningitis is greatest. Conjugate vaccines are dramatically reducing the global burden of disease caused by Nm, Spn and Hib, but their global uptake and impact needs to be enhanced, says the WHO.

Vaccine development: Focus on GBS

However, not all serogroups/types are covered by today's vaccines. No vaccine yet exists for the prevention of GBS disease: but there are candidates in development.

GBS is recognised as an important pathogen causing sepsis and meningitis in neonates. Maternal colonization by GBS is also a recognised cause of stillbirth and is the primary risk factor for GBS infection in neonates. Although rates are highest in the newborn and peripartum periods, GBS is an important cause of meningitis and sepsis in older adults and immunosuppressed subjects.

GBS vaccines in development include candidates from Pfizer (6 valent conjugate vaccine: serotypes Ia,Ib,II,III,IV,V. All conjugated to CRM197); and Minervax (Protein vaccine (Alpha C and Rib)). Both these vaccines are in mid-stage clinical trials.

The WHO wants to see the regulatory pathways for licensure of GBS vaccines defined by next year; and at least one affordable GBS vaccine licensed and WHO prequalified for material immunization during pregnancy by 2026. By 2030, it wants such a vaccine to be available in at least 10 countries.   

Improving existing vaccines

Beyond GBS, several Nm and Spn conjugate vaccine candidates are also in late-stage development, including multivalent products with broader serogroup/type coverage than existing vaccines. In addition, protein vaccine candidates against Nm, Spn and GBS are in various stages of development.

Examples of vaccines in clinical trials include:

Mn: GSK's '5-in-1' MenABCWY vaccine candidate entered Phase 3 trials in August 2020
Mn: Serum Institute's pentavalent ACWYX Conjugate Vaccine published Phase 2 results in June 2021
Mn: Pfizer's pentavalent meningococcal vaccine candidate, MenABCWY, started a Phase 3 study in June 2020

vaccines against meningococcal disease

The first polysaccharide vaccines against meningococcal disease were developed in the 1940s followed in the 1990s by the more effective conjugate vaccines.

Conjugate vaccines are now used in high-income countries as a component of the national immunization programmes in monovalent (A, C) or multivalent formulations (AC, ACY, ACW, ACYW). 

Polysaccharide vaccines continue to be sourced for global vaccine stockpiles to support an outbreak response through the International Coordination Group (ICG). In addition, some countries use polysaccharide vaccines as part of their routine immunization programmes for at-risk populations. 

Novel protein-based vaccines against meningococcal B disease are now being used at a public-health scale in some countries.

Some of the current concerns and/or gaps in the development of meningococcal vaccines to prevent meningitis include:

lack of a vaccine against the group X meningococcus, in development;
lack of quality-assured polysaccharide products;
lack of affordable conjugate products (multivalent) and B protein vaccines for low income countries; the demand is not clear globally from all market segments as many countries have chosen a high-risk, target population approach to meningococcal vaccine programmes, or rely on using vaccines only for outbreak response;
further development of global policy for optimal use, including strategies for epidemic response and optimal vaccine schedules;
further documentation of vaccine effects on meningococcal carriage and transmission patterns in different settings;
further assessment of correlates of protection.

Source: Defeating meningitis by 2030: baseline situation analysis, 2019 

Vaccines as a key strategic priority against antimicrobial resistance

The development and availability of distribution of meningitis vaccines also has another advantage: less cases of the disease require reduced use of antibiotics.

"As the high usage of antibiotics in the treatment of suspected meningitis can lead to the development of antimicrobial resistance, enhanced and sustained vaccination programmes being developed under the Immunization Agenda 2030 will have an increasingly important role in strategies for mitigating the negative impact of antimicrobial resistance. National plans should include vaccines as a key strategic priority or as a first line of defense against antimicrobial resistance in organisms that cause meningitis."

The size of the challenge

Despite 'significant progress' in reducing the incidence of meningitis over the past 20 years, there were still an estimated 5 million new cases globally and 290,000 deaths from meningitis in 2017, according to the WHO.

"Although meningitis affects all ages, young children are most at risk with around half of cases and deaths occurring in children under 5 years of age. Meningitis and meningitis-related sepsis can result in severe after-effects, such as hearing loss, visual and physical impairment, cognitive disability and limb loss."

The WHO has set a vision of 'Towards a world free of meningitis' - a tagline that recognises the challenges involved.

"Because meningitis has so many causes, it cannot be eliminated or eradicated," it explains. "There will be no "world free" moment for meningitis, but we are committed to get as close as possible.

"Our plan, therefore, aims to defeat meningitis as a public health threat, reducing the number of cases substantially and keeping them down." 

Immunization