Sex, Gender, and Vaccines: Considerations for COVID-19 Vaccine Immunity

View the original blog post on the Medicines, Technologies, and Pharmaceutical Services (MTaPS) Program website.

Monitoring patients who are taking a new medicine, including vaccines, is critical for patient safety. This type of monitoring, also known as pharmacovigilance (PV), helps detect, assess, understand, and prevent adverse effects of a medicine-related problem. PV is critical for determining the true safety and efficacy of a product, including identification of good and bad effects. USAID MTaPS supports low- and middle-income countries in building or strengthening PV systems and developing capacity to generate, analyze, and use safety data to improve health outcomes and the quality of care.

With the rapid introduction of the new COVID-19 vaccines, PV is an important aspect of the vaccine roll-out. Although safety is always the first concern with new medicines, it is well known that males and females respond to vaccines very differently. Therefore, we need to understand the difference between sex and gender:

• Sex is defined as male, female, or intersex and is based on sex chromosome complement, reproductive tissues (ovaries or testes), and sex steroid hormones (estrogen, progesterone, and testosterone). Hormones play an important role in vaccination.
• Gender is defined as the socially constructed roles, behaviors, activities, and attributes that a given society considers appropriate for males and females. Gender includes the binary designation, such as woman or man, and sexual and gender minorities.

It is important to understand that both sex and gender impact vulnerability, exposure risk, and treatment and response, which affects incidence, duration, severity, morbidity, mortality, and disability of emerging infectious diseases like COVID-19. They also play important roles in vaccine PV.

When it comes to immunity from vaccines, females are Superwomen.

When females are challenged with a vaccine, they mount a much better immune response to the vaccine because they have higher innate immunity responses to antigen stimulation. Therefore, females create higher titers of antibody to a vaccine.

Females also exhibit better efficacy (the percentage reduction in disease incidence in a vaccinated population), which means lower rates of hospitalization and mortality in older females when compared to males.

However, females aren’t Superwomen when it comes to reactions.

With better immunity comes more adverse reactions when compared to males. In early PV data from the COVID-19 vaccine in the United States, nearly 80% of reported reactions occurred among females (assigned female at birth), even though only 61% of vaccine doses were given to females. And this is common among many vaccines, not just the new COVID-19 vaccines.

Our immunity levels don’t stay the same forever.

With age, females lose Superwomen status. This is especially true for females who are 65 years and older. Antibody responses are lower in both males and females compared with younger adults, which is why there are high-dose forms of some vaccines.

As males and females age, hormones decline and so does immune function. Immune responses may also change with supplementation of hormone therapy, such as in post-menopausal persons, gender transition, or those with reproductive cancers.

We cannot forget pregnant individuals.

Pregnant people, too, have a different hormonal make-up, which also can significantly alter immune responses to vaccines. Pregnancy lowers immune regulation and creates poor immunologic responses compared to non-pregnant individuals.