September 22, 2023

Study assesses duration of protection offered by smallpox infection and possible cross-reaction with Mpox virus


More than 43 years ago, many Chinese residents were vaccinated with the vaccinia virus Tiantan strain (VTT) to protect them from smallpox infection.

Study: Duration of humoral immunity from smallpox vaccination and its cross-reaction with Mpox virus. Image Credit: Dotted Yeti/

A recent Signal Transduction and Targeted Therapy study assessed the level of immunity against smallpox in the aforementioned group of individuals. The level of immunological susceptibility to the mpox virus (MPXV) was also determined.


Mpox (previously known as monkeypox) disease is caused by the MPXV, which manifests similar symptoms to smallpox including fever and rash.

MPXV belongs to the Orthopoxvirus genus of the Poxviridae family. This virus is genetically close to Orthopoxvirus viruses, such as cowpox virus (CPXV), vaccinia virus (VACV), and variola virus (VARV).

In comparison to smallpox, mpox disease is less virulent with a lower mortality rate. In Mpox disease was first detected in the Democratic Republic of the Congo (DRC) in 1970.

As of June 21, 2023, around 88,026 mpox cases have been reported across 111 countries. In the UK, the first mpox case was detected on May 6, 2022; subsequently, a rapid transmission of this virus was recorded. The World Health Organization (WHO) declared mpox disease to be a public health emergency of international concern.

VACV-based vaccination was found to be extremely effective against smallpox and exhibited 85% efficacy against MPXV infection as well. Following the global eradication of smallpox infection in 1980, the routine smallpox vaccination has been discontinued in many countries.

This implies that people below 43 years of age who were not offered the smallpox vaccine are highly susceptible to orthopoxviruses, such as CPXV and MPXV infection.

In contrast, those above 43 years of age who received smallpox vaccination are potentially protected against CPXV and MPXV infection. The possibility of a decline in vaccination-induced immunity, over the years, must also be considered.

At present, two smallpox vaccines JYNNEOS and ACAM2000 are used to prevent mpox. These vaccines were approved by the US Food and Drug Administration (FDA) in 2019 to be used for adults at a higher risk of mpox and smallpox infections.

ACAM2000 is a second-generation smallpox vaccine and JYNNEOS is a third-generation vaccine. Although JYNNEOS is safer with limited side effects than ACAM2000, the former exhibited poor replicating ability in human cells. Neither vaccine provides absolute protection as previous studies have reported the incidence of breakthrough infection.

About the study

Following WHO’s recommendation, the Chinese government stopped the national smallpox vaccination program in 1981. Considering the current scenario, the current study determined the duration and extent of residual immunity to smallpox in individuals who received VTT vaccination around 43 years ago.

A total of 294 individuals were recruited in this study, whose ages ranged between 19 and 63 years. Based on their age, participants were divided into three groups. The first group consisted of 184 participants between the age of 19 and 42 years born post-1981, i.e., after routine smallpox vaccination.

The second group comprised 66 participants between 43 and 53 years of age with a history of smallpox vaccination between 1970 and 1980. The third group included 44 participants whose ages were between 54 and 63 years.

The vaccinia-specific level of residual humoral immunity was assessed in all participants in this study. In addition, neutralizing antibody titer, and vaccinia-specific IgG level was also determined.

The cross-antibodies of MPXV A29L, A35R, B6R, and M1R were assessed to understand whether remote smallpox vaccination provides protection against MPXV infection.

Study findings

The immunity levels of vaccinated individuals have decreased over time. However, unvaccinated individuals were more susceptible to mpox infection. Notably, humoral immunity was detected in those with VTT vaccination.

This finding implies that humoral immunity from smallpox vaccination persists in the Chinese population over 43 years of age; however, VTT-specific NAb level declines with age.

People with low or no VTT-specific antibodies are susceptible to MPXV upon exposure, which indicates a need for vaccination to protect people from mpox infection. In the current study, VTT-specific IgG was detected.

The number of plasma samples with positive VTT-specific IgG increased with age, implying that the majority of the participants born before 1981 still retained the binding antibody response to vaccinia after vaccination. 

It must be noted that the positive rate of anti-VTT NAb was marginally lower in people aged 54–63 years than in those aged 43–53 years. This finding indicates that in the current population, those who received smallpox vaccination decades ago, retained humoral immunity against VTT, particularly as high antibody levels targeting the A35R or B6R antigen were observed.

The plasma samples positive for VTT were also positive for three more antigens of A35R, B6R, and A29L. However, the levels of anti-M1R were relatively low in all participants.


The current study underscored the importance of smallpox vaccines in preventing mpox infection. Most Chinese individuals who received the VTT vaccine prior to 1981 still exhibited the presence of VTT-specific IgG antibody and could provide mpox virus-specific IgG antibodies.

This study recommends prioritizing the anti-MPXV strategy for individuals under the age of 43 years, particularly those who are at a higher risk of mpox infections.

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