Oom Aaron L, Wilson Kesi K, Yonatan Miilani, Rettig Stephanie, Youn Heekoung Allison, Tuen Michael, Shah Yusra, DuMont Ashley L, Belli Hayley M, Zucker Jane R, Rosen Jennifer B, Herati Ramin Sedaghat, Samanovic Marie I, Duerr Ralf, Kottkamp Angelica C, Mulligan Mark J
New York University Langone Vaccine Center, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.
Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J Virol. 2025 Mar 31:e0025325. doi: 10.1128/jvi.00253-25.
The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, public health officials began vaccination campaigns using the third-generation orthopoxvirus vaccine modified vaccinia Ankara from Bavarian Nordic (MVA-BN). Prior to this outbreak, the durability of monkeypox virus (MPXV)-specific immunity induced by MVA-BN was poorly understood. In 2022, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI, NCT05654883), a longitudinal study of 171 participants comprising MVA-BN vaccines and mpox convalescent individuals. Peripheral blood sampling was performed at intervals including prior to vaccination, after one dose, and after the second dose. MVA-BN vaccinees with and without a history of smallpox vaccination demonstrated detectable MPXV-specific memory B cells at 1-year post-vaccination. Additionally, MVA-BN increased MPXV neutralizing titers in smallpox vaccine-naïve vaccinees, with a comparable maximum titer reached in naïve and smallpox vaccine-experienced vaccinees. However, neutralizing titers returned to baseline within 5-7 months for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generated robust IgG responses against MPXV H3 and A35, but naïve vaccinees' IgG responses showed lower avidity than experienced vaccinees. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This work supports the need for long-term studies on protection induced by MVA-BN, including the potential need for booster doses as well as the development of next-generation orthopoxvirus vaccines.
The ongoing outbreaks of mpox demonstrate the continuing threat of orthopoxviruses to global health. While previous orthopoxvirus vaccines generated lifelong antibody and cellular immunity, we show here that the current mpox vaccine, MVA-BN or JYNNEOS, fails to induce durable antibody immunity in individuals with no prior smallpox vaccination. This raises the important question of whether MVA-BN vaccinees have long-term protection from mpox. Our work highlights the need for further studies into the durability of protection generated by MVA-BN as well as whether subsequent booster doses are necessary to maintain protection.
2022年全球IIb分支猴痘疫情是非洲国家以外首次大规模猴痘疫情。为控制疫情，公共卫生官员开始使用来自巴伐利亚北欧公司的第三代正痘病毒疫苗——改良安卡拉痘苗（MVA - BN）开展疫苗接种运动。在此次疫情之前，人们对MVA - BN诱导的猴痘病毒（MPXV）特异性免疫的持久性了解甚少。2022年，我们启动了纽约市猴痘免疫观察研究（NYC OSMI，NCT05654883），这是一项对171名参与者的纵向研究，包括接种MVA - BN疫苗者和猴痘康复者。在包括接种前、接种一剂后和接种第二剂后等不同时间点进行外周血采样。有和没有天花疫苗接种史的MVA - BN疫苗接种者在接种后1年都表现出可检测到的MPXV特异性记忆B细胞。此外，MVA - BN提高了未接种天花疫苗的疫苗接种者的MPXV中和滴度，未接种天花疫苗者和有天花疫苗接种史者达到的最大滴度相当。然而，未接种天花疫苗者的中和滴度在5 - 7个月内恢复到基线水平，而有过天花疫苗接种史者的中和滴度仍保持升高。未接种天花疫苗者和有过接种史者均产生了针对MPXV H3和A35的强烈IgG反应，但未接种天花疫苗者的IgG反应亲和力低于有过接种史者。这些数据突出了MVA - BN引发的低亲和力抗体反应，这种反应在未接种天花疫苗者中持续时间较短。这项工作支持了对MVA - BN诱导的保护作用进行长期研究的必要性，包括可能需要加强剂量以及开发下一代正痘病毒疫苗。
持续的猴痘疫情表明正痘病毒对全球健康的持续威胁。虽然以前的正痘病毒疫苗能产生终身抗体和细胞免疫，但我们在此表明，目前的猴痘疫苗MVA - BN或JYNNEOS未能在没有先前天花疫苗接种的个体中诱导持久的抗体免疫。这就提出了一个重要问题，即接种MVA - BN疫苗的人是否能长期预防猴痘。我们的工作强调了有必要进一步研究MVA - BN产生的保护作用的持久性，以及后续加强剂量是否对维持保护作用是必要的。
