Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals

Abstract

In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia Ankara—Bavarian Nordic (MVA-BN, also known as Imvamune, JYNNEOS or Imvanex) is a third-generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there are no data showing MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals nor vaccine efficacy against MPX. Here we show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a two-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, we conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.

Breakthrough monkeypox infection among individuals previously immunized with smallpox or monkeypox vaccination

“…These breakthrough infections are possibly caused by the short time between vaccination administration and infection, given the low titer of neutralizing antibodies expected following a single-dose administration. 9 All in all, this case-series reinforces the idea that individuals previously vaccinated against smallpox require a booster dose and the need for administration of a full two-doses monkeypox vaccination for unimmunized individuals, together with providing adequate counselling, in a scenario of limited available data, on the possible risk of breakthrough infections. 10 …”

“… 3 , 4 , 5 , 6 , 7 Moreover, individuals belonging to key-populations are currently receiving vaccines licensed against monkeypox, but preliminary data suggest that administration of the second dose is crucial for the effective development of neutralizing antibodies. 8 , 9 …”

Monkeypox

“…Monkeypox virus infection stimulates humoral and cellular immune responses that restrict viral replication and induce long-term immunity in recovering patients. 4 , 64 , 65 , 66 , 67 , 68 Humoral immune response after natural infection with monkeypox or vaccinia virus vaccination consists of orthopoxvirus-specific IgM and IgG antibodies against multiple antigen targets with long-term persistence of residual IgG-memory B cells 4 , 65 , 67 that protects from reinfection or from developing severe disease. 4 After vaccinia virus vaccination, specific memory B cells can last for decades, although only 50% of individuals have protective concentrations of neutralising antibodies after 20 years.…”

“… 147 However, lower levels of monkeypox-specific neutralising antibodies have been found in one study. 65 …”

Accumulation of immunity in heavy-tailed sexual contact networks shapes monkeypox outbreak sizes

“…Vaccine supplies were initially limited, slowing rollout of mass vaccination and precluding many countries from achieving substantial coverage before observing a peak ( 12, 13 )—moreover, time required for eligible individuals to complete the dosing schedule (e.g. 2 doses 4 weeks apart for JYNNEOS vaccine in the US ( 14 )) and for immunity to be established (suggested to be up to two weeks by public authorities ( 15 ) although evidence remains limited ( 16 )) renders prompt epidemic control by vaccination more challenging. Providing a coherent explanation to the observed decline in growth in many affected countries at different times and outbreak sizes is not straightforward.…”