最後一次愛滋病毒疫苗試驗失敗，科學家重新集結
Marcia Frellick / 2023 年 12 月 18 日 / Medscape 醫學新聞
在研究人員宣布該試驗「幾乎沒有機會」顯示疫苗為有效後，在非洲測試兩種實驗性愛滋病毒預防方案的 PREP 疫苗試驗已停止。專家表示，這次2b期試驗是這一代疫苗開發的最後一次嘗試，該疫苗使用了非中和抗體，科學家將不得不重新開始。
國際愛滋病協會（IAS）執行董事比爾吉特·波尼亞托夫斯基（Birgit Poniatowski）在聲明中表示：「我們不能也不會失去希望，世界將擁有一種有效的愛滋病毒疫苗，讓所有需要它的人在任何地方都能獲得這種疫苗。」
這項由非洲主導、歐洲支持的愛滋病毒預防研究自 2018 年以來一直在烏干達、坦尚尼亞和南非的四個地點開展，共有 1,513 名 18-40 歲的參與者參與。這項疫苗試驗正在測試兩種旨在預防愛滋病毒的實驗性組合方案和一種新形式的暴露前預防(PREP) 試驗，PREP試驗將持續進行。
據 IAS 稱，全球 3,900 萬名愛滋病患者中有近 2,100 萬人生活在東部和南部非洲的試驗點地區。
總部位於西雅圖的 HIV 疫苗試驗網絡的病毒學家兼首席研究員 Larry Corey 醫學博士告訴 Medscape Medical News，這一消息並不令人意外，因為最近兩項測試非中和抗體的 HIV 研究顯示缺乏療效。
但這次試驗的結果可能有助於回答一個問題。他解釋說：「有一小部分人對我們稱為 V1V2 循環的病毒部分具有非常高的免疫反應。」，「但是，出現這種免疫反應的人的頻率僅佔總人口的8%-10%。如果使用不同載體的這項試驗能顯示出相同的結果，那麼我們就必須花費更多的時間來製造一種免疫原，該免疫原能夠獲得100% 的人達到可能與 V1V2 循環相關的免疫力水平之免疫反應，則我們亦會帶著對下一步該做什麼的深刻見解走出這個困境。」
他說，到目前為止，致力於開發疫苗的科學家尚未確定針對病毒的哪一部分。
「臨床試驗做得非常好，這就是成功，」科里說。但「我們要從中吸取教訓嗎？」
HIV 疫苗的缺乏繼續地讓患者和科學家們感到沮喪，特別是因為針對其他疾病（例如 COVID-19）的疫苗已經以創紀錄的速度開發出來。但他解釋說，COVID-19 為疫苗開發帶來了完全不同的挑戰。
他說：「我們對愛滋病毒所做的努力比對新冠病毒所做的努力要困難得多。」，「新冠疫苗可以防止你生病；但你仍然會被感染。對於愛滋病毒，你必須先防止某人被感染。這需要更多的抗體和更好的免疫反應。」
他指出，儘管還有其他預防愛滋病毒的工具，但疫苗是實現全球消除愛滋病毒目標的唯一途徑，並指出愛滋病毒感染風險最高的人群「在過去15 年裡，其發生率都沒有變化為每年4 %。」
科里說：「我們距離結束愛滋病毒流行還差得很遠。」，「我們不會實現 2030 年目標，而我們無法實現 2030 年目標的原因之一是，全球 40% 到 50% 的愛滋病毒感染者是那些自我認定上並不自覺自己為感染高風險的人。」
這就是 PREP 的局限性，它已經存在了近二十年。它依賴愛滋病毒高風險族群的接受、攝取和堅持。「但口服 PREP 的情況非常糟糕，」他說。
有長效抗反轉錄病毒藥物或長效單株抗體。但他指出，從成本和努力的角度來看，這些措施也將集中在那些認為自己屬於高風險的人。「但在一些國家，你可以證明幾乎每個人都是高風險。」
他說，我們要真正能控制人口中疾病的唯一方法是使用疫苗。「僅僅因為它很難，並不意味著你應放棄。所有數據都顯示你必須擁有它。」
引用此內容：「最後一次 HIV 疫苗試驗失敗，科學家重新集結」 – Medscape – 2023 年 12 月 18 日。
Last of the HIV Vaccine Trials Fails, Scientists Regroup
Marcia Frellick / December 18, 2023 / Medscape Medical News
The PREP vaccine trial testing two experimental HIV prevention regimens in Africa has been stopped after investigators announced that there is “little to no chance” the trial will show the vaccines are effective.
This phase 2b trial was the last attempt in this generation of vaccine development, which has used non-neutralizing antibodies, experts say, and scientists will have to begin anew.
“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement.
The African-led, European-supported HIV prevention study has been running since 2018 at four sites in Uganda, Tanzania, and South Africa and has involved 1513 participants aged 18-40 years. The vaccine trial was testing two experimental combination regimens designed to protect against HIV and a new form of pre-exposure prophylaxis. The PREP trial will continue.
Almost 21 million of the 39 million people in the world with AIDS live in the test-site region of eastern and southern Africa, according to the IAS.
The news isn’t a huge surprise, as the last two HIV studies testing non-neutralizing antibodies showed a lack of efficacy, Larry Corey, MD, virologist and principal investigator of HIV Vaccine Trials Network, headquartered in Seattle, told Medscape Medical News.
But the results of this trial may help answer a question. “There is a small group of people who have really high immune responses to a part of the virus we call the V1V2 loop,” he explained. “But the frequency of people with that immune response is only 8%-10% of the population. If this trial, using a different vector, shows the same thing, then we have to spend a lot more time making an immunogen that gets 100% of the people to the levels of immunity that might be correlated with the V1V2 loop, and we’d walk out of this with a really good insight as to what to do next.”
So far, he said, scientists working to develop a vaccine haven’t determined which part of the virus to target.
“The clinical trial was very well done, and that’s the success,” Corey said. But “are we going to learn from it?”
The lack of an HIV vaccine continues to frustrate patients and scientists, especially because vaccines for other diseases, such as COVID-19, have been developed at record speed. But COVID-19 presented a completely different challenge for vaccine development, he explains.
“We’re doing something much harder with HIV than we did with COVID,” he said. “COVID vaccines prevent you from getting sick; you still get infected. With HIV, you have to prevent someone from getting infected in the first place. And that requires way more antibody and a way better immune response.”
Although there are other prevention tools for HIV, a vaccine is the only way to meet global elimination goals, he noted, pointing out that people who are at the highest risk for HIV “have an unchanged incidence over the past 15 years of 4% a year.”
“We are nowhere close to ending the HIV epidemic,” Corey said. “We’re not going to meet the 2030 goal. And one of the reasons we’re not going to meet the 2030 goal is that between 40% and 50% of the cases of HIV globally are in people who don’t self-identify as high risk.”
That’s the limitation with PREP, which has been available for nearly two decades. It counts on the acceptance, intake, and adherence of people at a high risk for HIV. “That has been abysmal with oral PREP,” he said.
There are long-acting antiretrovirals or long-acting monoclonal antibodies. But from a cost and effort standpoint, those would also be focused on people who consider themselves high risk, he pointed out. “In some countries, you could make a case that everybody’s high risk.”
The only way we’ve really ever controlled a disease on a population base is with a vaccine, he said. “Just because it’s hard, doesn’t mean you give up. All the data say you’ve got to have it.”
Cite this: Last of the HIV Vaccine Trials Fails, Scientists Regroup – Medscape – December 18, 2023.