Mix-and-Match: Why We Need More Flexibility in COVID-19 Vaccination Protocols

Many countries, including Bolivia, have extremely rigid COVID-19 vaccination protocols. These were developed based on the original trial data for each vaccine. The first vaccine you get is pretty much randomly assigned to you, based on which one is available at the time and location, when your age group is eligible to receive it. This seems to work pretty well. However, the second shot must be from the same provider, and you should get it within a short window of time, as determined by the protocol; which can be a logistical challenge both for people and health systems.

In Bolivia, for example, we just received a big shipment of Sinopharm vaccines, but people are clamoring for their Sputnik-V second dose, which for many is due now, according to the first shot vaccination certificate they received. At this time, Bolivia has a stock of more than 1 million COVID-19 vaccine doses, but it is a huge challenge to get them to the right people, at the right place, at the right time, according to the protocols.

It could potentially speed up the global vaccination roll-out if we allowed people to get their second shot from a different provider, which is why many clinical trials are currently underway testing the effects of mixing vaccines. Below we will provide a short overview of the evidence to date.


Scientific Evidence on Mixing and Matching COVID-19 Vaccines

The mix-and-match strategy, formally known as “heterologous prime and boost”, makes theoretical sense as it stimulates the immune system in different ways. The strategy has been widely used for the administration of HIV vaccines, and has been shown to increase the intensity and breadth of immune responses. Experiments in mice using different combinations of Chinese COVID-19 vaccine candidates indicated that heterologous sequences stimulated stronger antibody and T-cell responses than when applying the same type of vaccine twice. An adenovirus vectored vaccine followed by an mRNA vaccine provided a particularly strong antibody response in this trial (1).

The CombiVacS trial carried out in Spain was the first to test and publish results on this mixing strategy in humans. They found that the adenovirus vectored AstraZeneca vaccine followed by the Pfizer-BioNTech mRNA vaccine showed a very strong immune response with no alarming side effects (2). A small study in Germany also found this sequence to be safe and at least as potent as the homologous vaccination regiments (3).

The much larger ongoing randomized controlled Com-COV trial led by the Oxford Vaccine Group in the UK just came out with their first mixed schedule immunogenicity results this week. They found that the heterologous sequences (AZ-Pfizer and Pfizer-AZ), with a 28-day interval between prime and boost, produce far more antibodies than two AZ doses with the same interval, but not as many as two Pfizer doses (4). They are continuing to test the results of longer prime-boost intervals, and have also added other vaccines into the mix, including those more accessible for poorer countries, and more results will be coming out over the next few months.

It is worth pointing out that Sputnik-V was actually designed as a heterologous prime and boost vaccine, exactly because that makes theoretical sense. It uses two different recombinant adenovirus carriers (Ad-24 for the first shot and Ad-5 for the second one) in order to avoid that the primed immune system eliminates the carrier too quickly during the second shot, thus interfering with the immune response. This has shown to be a very effective strategy, and the use of two different vectors can also help overcome problems of pre-existing adenovirus immunity in the population (5).


Vaccine Mixing in Other Countries

Several European countries (e.g. Germany, France, Sweden, Norway, and Denmark), are already recommending that people who received the AstraZeneca vaccine for their first shot, should receive another vaccine for the second one. That is mainly due to the concern over rare side-effects of the AstraZeneca vaccine, but now it also appears that the mixing strategy produces a better immune response.

Given how important vaccine mixing could be in speeding up the global vaccine roll-out, I hope authorities are paying close attention to the results of these mixing trials, and will update protocols accordingly. If more experiments are needed, I will happily volunteer to mix my first AstraZeneca shot with any other available COVID-19 vaccine.



[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009122/

[2] https://www.isciii.es/Noticias/Noticias/Paginas/Noticias/Presentaci%c3%b3n-resultados-preliminares-CombivacS.aspx

[3] https://www.medrxiv.org/content/10.1101/2021.05.30.21257971v1

[4] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014

[5] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00191-4/fulltext


* SDSN Bolivia.

The viewpoints expressed in the blog are the responsibility of the authors and do not reflect the position of their institutions.

The First Diagnostics and Planning Workshop of SDSN Bolivia was successfully carried out!

On November 8, 2018, SDSN Bolivia carried out its First Diagnostics and Planning Workshop. Almost 40 representatives from member institutions came together to discuss the main structural obstacles and problems that Bolivia face, with the aim of prioritizing the work of SDSN Bolivia in the coming years.

The general consensus of the working groups was that Quality Education; Economic Growth and Decent Work; Health and Wellbeing; and Peace, Justice and Solid Institutions, are the most critical goals for Bolivia. For each of these goals, the groups discussed the main obstacles to reaching the goals, as well as possible solutions.

In addition, in order to establish a solid baseline for future work on the SDGs in Bolivia, SDSN Bolivia plans to produce an “Atlas of SDGs in Bolivia at the municipal level”, which is scheduled to be launched in November of 2019. This project will serve not only for SDSN, but for all institutions working on the 2030 Agenda, including the Central Government and sub-national governments. This is a huge undertaking and we invite all member institutions with expertise and interest to participate in the preparation of this Atlas.

The report on the First Diagnostics and Planning Workshop for SDSN Bolivia is available here:

Informe Primer Taller de Diagnóstico y Planificación de SDSN Bolivia 08112018


First Regional Meeting on Sustainable Development, Santa Cruz 2018

The Center for Human Development and Employability (CEDHE) at Universidad Autonóma Gabriel René Moreno in Santa Cruz is hosting the First Regional Meeting on Sustainable Development in Santa Cruz de la Sierra, 17-18 October, 2018. For more information and inscriptions, please consult the event page on facebook: https://www.facebook.com/events/718617938495959/

Fundación Alternativas

Fundación Alternativas (Alternativas)
Av. 20 de Octubre (entre Aspiazu y J.J. Pérez) Edif. 2034 – Of. 204
Phone: 591 2 2419061
Institutional web-site: https://alternativascc.org
Contact person: María Teresa Nogales, Executive Director
Contact e-mail: mtnogales@alternativascc.org

Fundación Alternativas is a Bolivian non-profit organization dedicated to promoting sustainable alternatives to guarantee food security in the cities of Bolivia. The work of Alternativas focuses on uniting civil, public and private efforts in designing and implementing public policies, programs and initiatives that permit citizens and communities to satisfy their universal right of alimentation. We work in three main areas: Food policy, socio-educational initiatives, and urban agriculture.

Avina Foundation Bolivia (AVINA)

Avina Foundation Bolivia (AVINA)
Av. Busch 281 – Edif. Rodrigo, Piso 1, Dpto. 1A, Santa Cruz de la Sierra, Bolivia
Phone: +591 3360014 / 3360011
Institutional web-site: www.avina.netwww.informeavina.org
Contact person: Miguel Castro Arze, Program Director
Contact e-mail:  miguel.castro@avina.net
Latin American Foundation aiming to produce large scale change in the direction of sustainable development for the region through the construction of processes of collaboration between diverse actors, and in that way contribute positively towards the SDGs.

Centro Boliviano De Estudios Económicos (CEBEC) de la Cámara de Industria, Comercio, Servicios y Turismo de Santa Cruz (CAINCO)

Centro Boliviano De Estudios Económicos (CEBEC) de la Cámara de Industria, Comercio, Servicios y Turismo de Santa Cruz (CAINCO)
Address: Av. Las Américas 7, Santa Cruz de la Sierra
Phone: +591-3-3334555.
Institutional web-site: www.cainco.org.bo
Contact persons: Pablo Mendieta and Patricia Hurtado
Contact e-mail: pablo.mendieta@cainco.org.bo, patricia.hurtado@cainco.org.bo
CAINCO is the largest business association in Bolivia. It encourages entrepreneurship and public policies for departmental, national and international development. It promotes innovation in the business and social fields.

Centro de Desarrollo Humano y Empleabilidad (CEDHE)

Centro de Desarrollo Humano y Empleabilidad (CEDHE) de la Facultad de Ciencias Económicas Administrativas y Financieras de la Universidad Autónoma Gabriel René Moreno
Address:  Ciudad Universitaria de la Av. Busch, entre segundo y tercer anillo. Módulo 244, segundo piso, Santa Cruz de la Sierra
Phone:  (+591) 76694294
Institutional web-site: www.facebook.com/cedhe.uagrm
Contact person:  Christian Andrés Aramayo Arce, Coordinator
Contact e-mail:  caramayoarce@gmail.com
The CEDHE promotes sustainable development through a portfolio of opportunities, strengthening soft and hard skills. Promotes and implements SDGs 4, SDG 8 and SDG 17.

Center for Participation and Sustainable Human Development (CEPAD)

Center for Participation and Sustainable Human Development (CEPAD)
Address:  Calle Raquel de Busch 69, Barrio Hamacas, Santa Cruz de la Sierra
Phone:  (+591-3) 3434192, 3434208
Institutional web-site: www.cepad.org
Contact person:  Rubens Barbery Knaudt, President
Contact e-mail:  rbarberyk@cotas.com.bo
The Center for Participation and Sustainable Human Development (CEPAD) provides support, assistance and guidance to both the public and the private sector on the topics of human development, economic development and sustainable development.

Centro de Investigaciones Agrícolas y Agroindustriales (CIAA)

Center for Agricultural and Agroindustrial Research (CIAA) / Universidad Privada Boliviana (UPB)
Av. Víctor Ustariz, km 6 ½, Zona Santa Rosa, Cochabamba, Bolivia
Phone: +591-4-4268287 (Int. 430)
Web-site: http://www.upb.edu/es/ciaa
Contact person: Carmen Carla Quiroga Ledezma, Ph.D., Director
Contact e-mail: : ccquiroga@upb.edu
The Center for Agricultural and Agroindustrial Research (CIAA) at UPB promotes the diversification of agricultural production, introduction of new appropriate techniques of industrial processing, improvement of productivity and competitiveness of high altitude agriculture, greater food security and conservation of biodiversity.

Centro de Investigaciones en Arquitectura y Urbanismo (CIAU)

Architecture and Urbanism Research Center (CIAU) / Universidad Privada Boliviana (UPB)
Av. Víctor Ustariz, km 6 ½, Zona Santa Rosa, Cochabamba, Bolivia
Phone: +591-4-4268287 (Int. 532)
Web-site: http://www.upb.edu/es/ciau
Contact person: Juan E. Cabrera, PhD. – Director
Contact e-mail: juancabrera@upb.edu
The Architecture and Urbanism Research Center was created with the following objectives: Implement, develop, execute and consolidate research projects in the areas of Architecture and Urbanism to help solve the needs of the region and the country in sensitive areas.