Grazing the pastures to achieve herd immunity

September 5, 2020 0 By FM

During this pandemic, nations have rushed to “flatten the curve,” a strategy that attempts to delay the inevitable and prevent healthcare systems from being overwhelmed. While a majority of nations imposed restrictions, Sweden embarked upon the lofty goal of achieving herd immunity. It was observed, however, that only 7.3% of the population of Stockholm had developed anti-SARS-CoV2 antibodies in a span of 3 months, showing that the path to herd immunity is not as straightforward as it seems.

Aside from natural infection, immunisation programmes usually play a crucial role in bringing about herd immunity in a population. Immunisation programmes can be thought of as a public health tool that aims to limit the countless threats imposed by pathogens. Vaccinations induce protective immunity by priming the immune system to debilitating pathogens, ensuring that upon natural exposure to the pathogen in the environment, the individual will develop an effective and complete immune response.

Herd immunity

Herd immunity refers to a phenomenon where individuals who have previously been infected with a pathogen or who have been vaccinated against a pathogen confer immunity to the remainder of the population. The latter comprises individuals who are more susceptible to infection. They may be immunologically naive, i.e. have never been exposed to the pathogen — either naturally or through vaccination — be immunologically compromised. Herd immunity can be thought of as a blanket form of immunity that stems from the individual level to the population level by virtue of lowered transmission level. When the transmission of a pathogen is no longer sustained, the spread of the infection will eventually cease. 

Epidemiologists have defined various parameters of transmission dynamics that enable policymakers to make informed decisions regarding the effectiveness of herd immunity on a pathogen. One such parameter is the basic reproduction number (Ro), which is defined as the average number of secondary infections caused by a single infectious individual introduced into a completely susceptible population. It is characterised by the nature of the pathogen and the population under consideration. The higher the value of Ro, the more communicable the pathogen and the higher the number of individuals that need to be immune to impede sustained transmission. The Ro value of SARS-CoV2 has widely been reported to be 3, indicating that approximately 67% of the population is required to acquire immunity in order for the effects of herd immunity to kick in. 

This assumption relies on theoretical factors like homogeneous mixing of individuals within the population and the establishment of life-long immunity. A deeper understanding of transmission dynamics is necessitated, as herd immunity must not only prevent the onset of clinical disease but also block the transmission of the pathogen. This would address issues such as the number of infectious viral particles that are required to cause infection and highlight the urgency to identify asymptomatic carriers. Collectively, this model shows significant risk in attempts to achieve herd immunity in the absence of a vaccine and a therapeutic agent and under the setting of finite healthcare resources.

Path towards a vaccine 

Herd immunity can only be realized by an immune response that possesses two key characteristics: the ability to provide complete protection and immunity that is life-long. Studies have reported that the SARS-CoV-2 spike protein elicits neutralising antibodies that remain in circulation for at least a month, offering protection against reinfection. This suggests that at least short-term immunity is generated. Upon reinfection, it is speculated that memory lymphocytes would limit the severity of the clinical disease. Thus far, reinfection with SARS-CoV2 has not been reported in humans. Although some studies have reported detection of viral RNA in recovered patients, this could be indicative of sporadic viral shedding, latent persistent infection, human error or reinfection. Collectively, reports suggest that the adaptive immunity towards SARS-CoV2 is likely to diminish over time, leading to annual or biennial outbreaks and suggests the need for booster vaccinations.

A disconcerting factor is the emergence of genetic drift variants and their contribution to severe disease. Genetic drift variants arise when viral RNA genomes mutate, leading to the generation of gene variants that could potentially possess altered immunogenic properties. Such variants have been reported in SARS-CoV2 isolates. This could enable the virus to escape from immune recognition or contribute to severe disease. For instance, the memory of a previous SARS-CoV2 infection may trigger the immune system to generate a partial immune response, where antibodies are unable to neutralise the virus particles. This leads to severe disease, marked by a cytokine storm, tissue damage and diminished antiviral response. This phenomenon is referred to as antibody-dependent enhancement (ADE) of infection. It is unclear whether ADE occurs in SARS-CoV2. However, it is of importance to vaccine design since vaccination could trigger severe disease in individuals who had previously been exposed to the virus under natural conditions. This indicates that vaccine development studies would need to carry out epitope mapping to include epitopes that are incapable of inducing ADE. These pieces of evidence emphasise the need for SARS-CoV2 post-infection immunity studies to aid in vaccine development. 

Additionally, it is important to recognise immunosenescence, the waning of the immune system and vaccine-induced immunity with age. It has been observed that the incidence and severity of vaccine-preventable diseases are higher in non-immunised adult population as a consequence of childhood-centric vaccine coverage. This detrimental herd effect is most likely due to immunosenescence in adults. The same applies to COVID-19, where severe disease has been observed in patients with advanced age. This indicates that it is important to ensure that vaccinations address all members of a population to ensure that protective herd immunity is applied across all lifespans. 

Onward journey

Taking into consideration the transmission dynamics and immunological factors, the journey to achieving herd immunity against this virus appears tumultuous. These are only some of the obstacles put forth by SARS-CoV2 in the path to the development of an “immune population” and a suitable vaccine candidate. It can, therefore, be reasoned that at this point of time, attempts to establish herd immunity cannot be considered as the primary objective of any health policy. Rather, it is prudent to ensure that the most vulnerable groups of the society are protected in the hope that herd immunity will be achieved as a by-product of these efforts.   

The author is a senior science writer. She holds a degree in biomedical science from the University of Adelaide and a Master of Science in medical biotechnology from Manipal Academy of Higher Education.