結核ワクチン、新型コロナに有効か　臨床試験で検証へ

【パリＡＦＰ＝時事】結核を予防するために数十年間にわたり利用されている一般的なワクチンが、新型コロナウイルス感染症（COVID-19）から医療従事者を守る助けになり得るだろうか──。（写真は資料写真）
　新型コロナウイルスに特化した予防接種が開発されるまでには、まだしばらく時間がかかると予想されている。そうした状況において、抗結核ワクチンＢＣＧが有する潜在的な有効性についての調査が進められている。ＢＣＧ接種は世界中で多くの人が子どもの時に受けている。
　ＢＣＧワクチンを接種している子どもは、ＣＯＶＩＤ-１９とは別の呼吸器疾患に罹患（りかん）しにくい。ＢＣＧまた、一部ぼうこうがんの治療にも用いられているほか、１型糖尿病などの自己免疫疾患やぜんそくなどの予防にも効果がある。
　そのため研究者らは、新型コロナウイルスに対しても、感染リスクの軽減や症状の重症化を抑えるといった効果がＢＣＧにあるかどうかを検証したい考えだ。
　仏国立保健医学研究所（ＩＮＳＥＲＭ）のカミーユ・ロクト氏はＡＦＰの取材に対し、ＢＣＧワクチンの全例接種が２００７年まで実施されていたフランスでは、「調査対象者の大半が初回のワクチン接種をすでに受けていることになる」と話した。ただ、その予防効果が時間とともに低下することにも触れた。
　ロクト氏は、ＢＣＧワクチンに何らかの効果が確認された場合は、ＣＯＶＩＤ-１９に対処する取り組みの最前線にいる医療従事者を「最初の対象」にすべきとの考えを示している。しかし、臨床試験の詳細について取りまとめを行っている同氏の考えとは逆に、ＢＣＧが予防効果をもたらすとの考えには依然として慎重な見方を示す専門家らもいる。
　そうした中でオランダ・ラドバウド大学が最近、同国のユトレヒト大学と協力して医療従事者数百人を対象とする臨床試験を実施すると発表した。ラドバウド大のミハイ・ネテア教授（実験内科学）は、「この調査を行う理由がまさにそれ（考え方の相違）だ」と話す。

■先天性免疫系を「訓練」
　オランダの臨床試験では、医療専門家ら５００人にＢＣＧを、５００人にはプラセボ（偽薬）をそれぞれ接種する。ネテア教授は、今回の流行期間中にＢＣＧワクチン接種グループでの感染者が少なければ、結果は有望と考えることができると述べる。
　臨床試験実施の発表に際してラドバウド大は、ＢＣＧワクチンが新型コロナウイルスを直接的に防ぐわけではなく、免疫系を高めることで抵抗力の向上と感染の軽減につながる可能性があると説明している。
　これは、特にＢＣＧや麻疹などのような病原性を低下させたウイルスがごくわずかに含まれる弱毒化ワクチンによって、攻撃に対してより効果的に対抗できるよう先天性免疫系を「訓練」して準備するイメージだ。
　ＣＯＶＩＤ-１９の場合、ウイルス自体の感染に加え、一部の患者では過剰な免疫反応が起こり「炎症性サイトカイン」と呼ばれるタンパク質の産生が制御不能となる。
　ＩＮＳＥＲＭのリサーチディレクターを務めるローラン・ラグロ氏は、「ワクチン接種、特にＢＣＧワクチンは、この炎症免疫反応の調整を改善する助けになる可能性がある」と述べる。同氏は炎症と免疫系の関連性に関する研究に取り組んでいる。
　この他、オーストラリアでも医療従事者約４０００人を対象とするＢＣＧワクチンの臨床試験が、豪小児医療研究所「マードック・チルドレンズ・リサーチ・インスティチュート」によって始まっている。【翻訳編集ＡＦＰＢＢＮｅｗｓ】
〔ＡＦＰ＝時事〕（2020/04/08-13:38）

Could a common vaccine used for decades to protect against tuberculosis help shield health workers from COVID-19?
While developing a specific immunisation against the coronavirus sweeping the planet will likely take many months, researchers are studying the potential benefits of the BCG shot, which many people around the world receive as children.
Laboratories and pharmaceutical firms are racing to find medicines to tackle COVID-19, which has infected more than a million people, killed at least 50,000 and for which there is currently no known treatment, vaccine or cure.
They are also looking at repurposing existing drugs.
- Experts remain cautious -
We have known for decades that BCG has non-specific beneficial effects, in that it protects against diseases other than the one for which it was created, Camille Locht, of the French public health research institute Inserm, told AFP.
Children vaccinated with BCG suffer less from other respiratory illnesses, it is used to treat certain bladder cancers and it could protect against asthma and autoimmune diseases such as type 1 diabetes.
Researchers want to test whether the tuberculosis vaccine could have a similar effect against the new coronavirus, either by reducing the risk of being infected, or by limiting the severity of the symptoms.
In France, where the BCG vaccine was compulsory until 2007, most of the study participants will have already had a first vaccination, but the protective effect of this decreases over time, said Locht.
Because healthcare workers are on the front lines of the efforts to tackle COVID-19, they should be the first target if there is any benefit found with the BCG vaccine, said Locht, who is finalising details for a clinical trial in France.
But experts remain cautious on the potential of the BCG to provide protection.
- 'Military exercise in peacetime' -
That is exactly the reason for this research, says Mihai Netea, professor of experimental internal medicine at Radboud University in the Netherlands, which recently announced a clinical trial, with the University of Utrecht involving hundreds of healthcare workers.
This will see 500 medical professionals receive the BCG jab and 500 get a placebo.
If during this epidemic fewer people in the BCG-vaccinated group would drop out due to illness, this would be an encouraging result, added Netea, a specialist in trained immunity.
This is a relatively new concept based on the discovery that our innate immune response -- the body's generalised defences -- also has a memory, alongside the acquired immunity, which develops antibodies after coming into contact with a specific pathogen.
The BCG vaccine does not directly protect against the coronavirus, but provides a boost to the immune system which may lead to improved protection and a milder infection, Radboud university said of the study.
The idea is that the innate immune system can be prepared, or trained to better combat attacks, thanks in particular to live attenuated vaccines, such as BCG or measles, which contained a weakened sliver of the original pathogen.
In the case of COVID-19, in addition to infection by the virus itself, some patients have also suffered excessive immune responses, with the uncontrolled production of pro-inflammatory proteins, cytokines.
Vaccination, in particular against BCG, might help to better orchestrate this inflammatory immune response, said Laurent Lagrost, Inserm research director who works on links between inflammation and the immune system.
The vaccine acts as a military exercise in peacetime so that the body can fight the enemy effectively in wartime, he said in an interview this week with French broadcaster BFMTV.
- International effort -
A separate trial of the BCG vaccine has also been launched in Australia, with some 4,000 health workers, by the Murdoch Children's Research Institute.
Microbiologist Locht wants to harmonise the criteria of the French study with that planned in four Spanish hospitals, in order to better compare their results.
However, researchers in Spain, instead of using the BCG, would like to try a new tuberculosis vaccine developed by the biotech firm Biofabri.
This vaccine candidate, whose safety has already been demonstrated, should offer better protection, said Carlos Martin, professor of microbiology at the University of Zaragoza, because it is developed from a strain isolated in humans.
In contrast, he said the BCG is prepared from a strain of the bacteria that infects cattle, and two genes very important to the virulence of tuberculosis have been deactivated in the vaccine candidate.
Another advantage of the new vaccine is that it is made in Europe and could be quickly made available, while the BCG suffers from strong supply tensions and using it for adults against COVID-19 could deprive children of it in countries where tuberculosis remains endemic.
In Germany, the Max Planck Institute for Infectious Biology is also preparing a trial with a genetically-modified vaccine candidate, developed by the Serum Institute of India.
In coordination with these countries, Inserm announced on Thursday that clinical trials could also be launched in Africa, where health systems are expected to come under acute pressure from the coronavirus pandemic.