Understanding Herd Immunity in the Context of HPV

Herd immunity (or community immunity) occurs when a sufficiently high proportion of a population becomes immune to an infectious disease, thereby limiting its spread. For a sexually transmitted infection like the Human Papillomavirus (HPV), achieving high vaccination coverage can dramatically reduce the viral reservoir in the population, offering protection even to those who are unvaccinated.

Vaccination Thresholds and Efficacy

The prophylactic HPV vaccines (such as Gardasil 9) are highly effective at preventing infection by the most oncogenic HPV genotypes, as well as the types that cause genital warts. Epidemiological modeling suggests that when vaccination coverage in target cohorts (typically early adolescents) reaches 70% to 80%, the transmission dynamics of the virus are severely disrupted. High coverage among females significantly reduces the transmission to males, and the inclusion of males in routine vaccination programs further fortifies this effect.

Cross-Protection Mechanisms

While current vaccines directly target up to nine HPV types, there is evidence of cross-protection against phylogenetically related high-risk types not included in the vaccine formulation. This immunological cross-reactivity provides a broader shield against cervical dysplasia and associated cancers, enhancing the overall public health impact of the vaccination programs.

Real-World Success: The Australian Model

Australia provides the leading global example of HPV herd immunity in action. By implementing a comprehensive, gender-neutral, school-based vaccination program, Australia achieved exceedingly high coverage rates. Within a decade, the country observed dramatic declines in genital wart presentations and significant reductions in high-grade cervical dysplasia among young cohorts. Australia is currently on track to be the first nation to effectively eliminate cervical cancer as a public health problem.

Challenges and Global Disparities

Despite these successes in high-income nations, significant challenges remain globally. Low- and middle-income countries (LMICs) bear the highest burden of cervical cancer mortality but often lack the infrastructure and resources to implement widespread vaccination programs. Achieving global herd immunity will require concerted international efforts to improve vaccine access and address vaccine hesitancy.

Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become immune to an infection, whether through previous infections or vaccination, that the communicable pathogen cannot maintain itself in the population, its low incidence thereby reducing the likelihood of infection for individuals who lack immunity.

Once the herd immunity has been reached, disease gradually disappears from a population and may result in eradication or permanent reduction of infections to zero if achieved worldwide. Herd immunity created via vaccination has contributed to the reduction of many diseases. Some individuals either cannot develop immunity after vaccination or for medical reasons cannot be vaccinated. Newborn infants are too young to receive many vaccines, either for safety reasons or because passive immunity renders the vaccine ineffective.

Individuals who are immunodeficient due to HIV/AIDS, lymphoma, leukemia, bone marrow cancer, an impaired spleen, chemotherapy, or radiotherapy may have lost any immunity that they previously had, and vaccines may not be of any use for them because of their immunodeficiency. A portion of those vaccinated may not develop long-term immunity. Vaccine contraindications may prevent certain individuals from being vaccinated.

In addition to not being immune, individuals in one of these groups may be at a greater risk of developing complications from infection because of their medical status, but they may still be protected if a large enough percentage of the population is immune. High levels of immunity in one age group can create herd immunity for other age groups.

Vaccinating adults against pertussis reduces pertussis incidence in infants too young to be vaccinated, who are at the greatest risk of complications from the disease. This is especially important for close family members, who account for most of the transmissions to young infants. In the same manner, children receiving vaccines against pneumococci reduces pneumococcal disease incidence among younger, unvaccinated siblings.

Vaccinating children against pneumococcus and rotavirus has reduced pneumococcus- and rotavirus-attributable hospitalizations for older children and adults, who do not normally receive these vaccines. Influenza (flu) is more severe in the elderly than in younger age groups, but influenza vaccines lack effectiveness in this demographic due to a waning of the immune system with age. The prioritization of school-aged children for seasonal flu immunization, which is more effective than vaccinating the elderly, however, has been shown to create a certain degree of protection for the elderly.

For sexually transmitted infections (STIs), high levels of immunity in heterosexuals of one sex induces herd immunity for heterosexuals of both sexes. Vaccines against STIs that are targeted at heterosexuals of one sex result in significant declines in STIs in heterosexuals of both sexes if vaccine uptake in the target sex is high. Herd immunity from female vaccination does not, however, extend to males who have sex with males.

High-risk behaviors make eliminating STIs difficult because, though most infections occur among individuals with moderate risk, the majority of transmissions occur because of individuals who engage in high-risk behaviors. For this reason, in certain populations, immunizing high-risk individuals may be necessary regardless of sex. Herd immunity itself acts as an evolutionary pressure on pathogens, influencing viral evolution by encouraging the production of novel strains, referred to as escape mutants, that are able to evade herd immunity and infect previously immune individuals.

The evolution of new strains is known as serotype replacement, or serotype shifting, as the prevalence of a specific serotype declines due to high levels of immunity, allowing other serotypes to replace it. At the molecular level, viruses escape from herd immunity through antigenic drift, which is when mutations accumulate in the portion of the viral genome that encodes for the virus's surface antigen, typically a protein of the virus capsid, producing a change in the viral epitope.

Alternatively, the reassortment of separate viral genome segments, or antigenic shift, which is more common when more strains are in circulation, can also produce new serotypes. When either of these occur, memory T cells no longer recognize the virus, so people are not immune to the dominant circulating strain. For both influenza and norovirus, epidemics temporarily induce herd immunity until a new dominant strain emerges, causing successive waves of epidemics.

As this evolution poses a challenge to herd immunity, broadly neutralizing antibodies and "universal" vaccines that can provide protection beyond a specific serotype are in development. Initial vaccines against Streptococcus pneumoniae significantly reduced nasopharyngeal carriage of vaccine serotypes (VTs), including antibiotic-resistant types, only to be entirely offset by increased carriage of non-vaccine serotypes (NVTs). This did not result in a proportionate increase in disease incidence though, since NVTs were less invasive than VTs.

Since then, pneumococcal vaccines that provide protection from the emerging serotypes have been introduced and have successfully countered their emergence. The possibility of future shifting remains, so further strategies to deal with this include expansion of VT coverage, and the development of vaccines that use either killed whole-cells, which have more surface antigens, or proteins present in multiple serotypes. If herd immunity has been established and maintained in a population for a sufficient time, the disease is inevitably eliminated – no more endemic transmissions occur.

If elimination is achieved worldwide and the number of cases is permanently reduced to zero, then a disease can be declared eradicated. Eradication can thus be considered the final effect or end-result of public health initiatives to control the spread of contagious disease.

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